With funding from Swim Across America – Boston, researchers at the Perini Family Survivors’ Center have developed innovative new protocols for treating long-term negative impacts of childhood cancer treatments, including sleep disorders, sexual dysfunction, and relationship challenges.
In April 2026, 30 Swim Across America – Boston (SAA-Boston) participants, volunteers, donors, and patients visited Dana-Farber Cancer Institute for presentations from five researchers, followed by a special tour of the Dana-Farber Cancer Institute (DFCI) facilities.
Researchers at the Perini Family Survivors’ Center use Swim Across America-Boston funds to test innovative new patient interventions and expand successful treatment protocols to culturally Latino communities
Director of Research Christopher Recklitis Ph.D., MPH, originally a Swim Across America Fellow at DFCI and who has swum the SAA-Boston event in Pleasure Bay, provided an overview of Project REACH, which encompasses a range of interdisciplinary, longitudinal studies targeting improved outcomes for survivors of childhood cancers. As more and more people survive childhood cancers, they form a growing population of patients who experience a wide variety of life-altering negative impacts of cancer treatment. Project REACH studies the unique cohort of DFCI
To date, Project REACH has published 21 peer-reviewed publications from 38 investigators and trainees, fulfilling two goals of expanding research while launching careers of the next generation of top research talent. As a result, at least 13 other major cancer institutions around the U.S. have investigators who were funded by Swim Across America at some point.
“SAA funding gives us the flexibility that no one else has to innovate when unexpected needs arise,” Dr. Recklitis explained. For example, in 2020, Project REACH used SAA funds to pilot a study of virtual treatment visits for survivors. The pilot began in April 2020, and they were able to publish the results in November of the same year. “Simply put, research never moves that quickly, primarily because funding requires more lead time. SAA funds enabled us to change course on a dime. Moreover, we were able to share our findings with practitioners around the world by publishing.”
Explaining her “Bridging the Gap” programs, Teresa Neira, PhD, LISCW explained the work she has been able to do to translate proven protocols to Spanish language and Latin cultural norms, making the benefits available to a significantly larger number of childhood cancer survivors. Dr. Neira explained that translating a treatment protocol is not simply about language, but also about cultural norms and points of reference. With cultural adaptations, Latino and Latina survivors are more open to and better able to access the benefits that are more readily available to English speaking Perini Center patients.
Director of the Perini Family Survivors’ Center Lisa Diller MD emphasized the flexibility that SAA-Boston funding enables. Since 2020, multiple SAA-funded researchers at DFCI have been able to secure large grants from the National Cancer Institute (NCI) by demonstrating promising results in a smaller Project REACH cohort. “These smaller test studies simply wouldn’t have been possible without the flexibility provided by SAA funds,” Dr. Diller said.
One such researcher, Lydia Chevalier, PhD, who also has swum the SAA-Boston event, opened by saying, “Swim Across America Fellowship completely changed the trajectory of my career.” In her fellowship, Dr. Chevalier found that, in her Project REACH respondent pool, 32% of the young adult cancer survivors (YACS) reported sexual dysfunction and 34% of YACS reported that they were sexually inactive. As one patient said to her, “How do you date when you’re scared to have sex?” SAA-Boston funding gave Dr. Chevalier the flexibility to shift her focus to deeply impactful work and secure a larger grant from the NCI.
Trainee Alexis Michaud (PhD candidate in Clinical Psychology) began working with Project REACH during the first year of her PhD program and developed one of her projects into her dissertation work. She is developing a Phase 2a proof of concept trial assessing the effectiveness of On-Trac, a brief online intervention to address anxiety to suit the particular needs of childhood cancer survivors, which are different from standard cognitive behavioral approaches. Michaud shared that the opportunity to do this level of research as a doctoral candidate was exceptional.
SAA-Boston visitors came away with a renewed sense of purpose and energy. As a twelve-year-old participant said, because of SAA-Boston funding, the Perini Center researchers “have seed money for the small ideas that turn programs into the standard of care at Dana-Farber, which other Cancer institutions mimic.” We are so proud to support this important work that benefits childhood cancer survivors.
For 15 years, Swim Across America has fueled innovative early-stage research at Fred Hutch Cancer Center and UW Medicine and helped launch the careers of dozens of young scientists. We’re proud to share details about the six most recent projects made possible through funds raised in 2022 and 2023 by Swim Across America – Seattle and the dedicated swimmers who participated. From improving patients’ quality of life to overcoming tumors’ resistance to immunotherapy, these innovative projects have the potential to dramatically enhance cancer treatment.
Inspired to Make Waves to Fight Cancer this year? Swim, volunteer or donate to SAA-Seattle at swimacrossamerica.org/seattle.
Kate Markey, MBBS, PhD, FRACP | Stem cell transplantation
Assistant Professor, Fred Hutch and UW Medicine
Project: Restoring the gut microbiome after blood stem cell transplant
Dr. Kate Markey
Background: Fred Hutch researchers have shown that while blood stem cell transplantation continues to be the most effective treatment for multiple myeloma, it can also severely damage patients’ gut microbiome, leading to strong gastrointestinal side effects and poor outcomes. Dr. Markey, a medical oncologist who studies the gut microbiome and its role in recovery from transplant, developed a study to examine whether a five-week, plant based, whole-food diet can restore patients’ beneficial gut bacteria and improve immune function and outcomes.
2024 progress statement: Dr. Markey and her colleagues opened the trial in October, and by the end of the following month they had enrolled seven patients, or one-third of their goal. They are collecting stool and blood samples and plan to analyze all of them once the trial is complete. If all goes as expected this summer they intend to use the resulting data to apply for a federal research grant to support a much larger, randomized clinical trial.
Alexandre Hirayama, MD | Blood cancers
Assistant Professor, Fred Hutch and UW Medicine
Project: Understanding how large B-cell lymphoma evades CAR T-cell therapy
Dr. Alexandre Hirayama
Background: Less than half of patients who undergo CAR T-cell therapy for large B-cell lymphoma (LBCL) enjoy long-lasting remission. We’re not sure why, but the answer may lie in the tumor microenvironment. There’s still so much we don’t know about this collection of cells, stroma, and blood vessels that surround and support the tumor, including how it might suppress cancer therapies. Dr. Hirayama, who specializes in treating patients with B-cell malignancies, is studying the tumor microenvironment in minute detail to help identify and explain how patients’ tumors may mute CAR T cells’ effectiveness.
2024 progress statement: Dr. Hirayama has gathered the necessary tumor samples for these studies and refined the techniques and technologies that will allow him to study immune, stromal, and tumor cells in the tumor microenvironment. He expects to begin studying the samples in summer 2025.
Diane Tseng, MD, PhD | Lung cancer
Assistant Professor, Fred Hutch and UW Medicine
Project: Reducing inflammatory effects of immunotherapy in patients with lung cancer
Dr. Diane Tseng
Background: Many patients with lung cancer who are treated with checkpoint inhibitors experience a condition called checkpoint inhibitor pneumonitis (CIP). If left untreated, CIP can cause irreversible damage. Recent research shows that immune cells called napsin A–specific T cells may be involved in mediating CIP. Dr. Tseng, an oncologist who specializes in treating patients with lung cancer, is working with McGarry Houghton, MD — a Fred Hutch and UW Medicine professor and holder of the Satya and Rao Remala Family Endowed Chair — to study napsin A–specific T cells’ role in CIP and exploring strategies for muting it.
2024 progress statement: Dr. Tseng’s work has focused on 1) developing a method for detecting napsin A– specific T cells in donor blood; 2) developing a method for taking those cells and growing more of them in the lab; and 3) creating a test to determine whether a different T cell can eliminate them. This work will establish the foundations for understanding the function of napsin A–specific T cells and the role they might play in CIP.
Emily Liang, MD | Blood cancers
Hematology/oncology Fellow, Fred Hutch and UW Medicine
Project: Mitigating serious side effects of CAR T-cell therapies in patients with blood cancers
Dr. Emily Liang
Background: While CAR T-cell therapy has revolutionized treatment for patients with blood cancers like lymphoma and multiple myeloma, it also comes with a high risk of fever, fatigue, body aches, and even neurologic impairment. Though these conditions are reversible, they can be life-threatening and prevent older and frailer patients from receiving CAR T-cell therapy at all. Dr. Liang, who specializes in acute leukemias and CAR T-cell therapy, and her mentor, Jordan Gauthier, MD, MSC, a Fred Hutch and UW professor and former Swim Across America funding recipient, want to make these treatments accessible to a wider range of patients. So, the pair launched a first of-its-kind trial to study whether a drug typically prescribed for rheumatoid arthritis called anakinra can prevent these inflammatory responses.
2024 progress statement: After treating more than 30 patients in their clinical trial, Drs. Liang and Gauthier found that prophylactic administration of anakinra did not seem to be effective in preventing cytokine release syndrome, a side effect associated with a high level of inflammation in the blood. However, prophylactic anakinra did seem to reduce the severity and duration of neurologic side effects as well as the need for steroids. Importantly, Drs. Liang and Gauthier also found that anakinra may impair the treatment’s effectiveness against tumors. Now, the pair are planning to study how anakinra mitigates inflammation in the brain, whether there may be alternative prevention strategies, and how anakinra impacts CAR T-cell function.
Saurav Kumar, PhD | Colorectal cancer
Postdoctoral Fellow, Fred Hutch
Project: Exploring new uses for existing drugs to treat colorectal cancer
Dr. Saurav Kumar
Background: Colorectal cancer is one of several cancers driven by a process called gene fusion, in which two independent genes combine incorrectly and begin producing proteins that can lead to cancer. And though a range of drugs have been developed to target these fusions and stop the mechanism that promotes cancer growth, they’ve so far been ineffective against colorectal cancer. However, Dr. Kumar, who studies metastasis, recently discovered that patients with colon cancer who receive TRK inhibitors (TRKi) experience a drop in TRK fusion protein levels, suggesting that these inhibitors may be degrading the cancer-causing fusion proteins. He plans to study the interaction that causes this protein degradation with the goal of one day using TRKi to create more effective therapies for patients with this form of cancer.
2024 progress update: Dr. Kumar and his colleagues have developed three protein degraders, called PROTACs, based on an FDA-approved TRKi. Now they plan to begin testing them on colorectal cancer cells in the lab to better understand the mechanism that leads to TRK fusion protein degradation — which could one day inform the development of targeted therapies for patients with these cancers.
Yapeng Su, PhD | Pancreatic cancer
Postdoctoral Fellow, Fred Hutch
Project: Overcoming solid tumors’ resistance to immunotherapies
Dr. Yapeng Su
Background: Pancreatic cancer is notoriously difficult to treat. Though we’ve found a protein on tumor cells that would seemingly make for a good immunotherapy target, treatments that have been studied and validated in the lab fail in patients — likely due to unique characteristics of the tumor microenvironment. Using technology that allows us to see the interaction of cells within tumors and better understand how they influence one another, Dr. Su, who studies adoptive cellular immunotherapy, is examining the mechanisms that cause immunotherapies to fail and exploring techniques to overcome them.
2024 progress statement: After completing a detailed study of samples from tumors previously treated with adoptive T cell therapy, Dr. Su found that they contained several cell types that were both potentially immunosuppressive and arranged in distinct patterns throughout the tumor microenvironment. He also identified several subtypes of T cells (whose role is to attack cancer cells) that no longer functioned properly. In the coming months, Dr. Su plans to further analyze the T-cell subtypes and their placement within the tumor microenvironment to better understand why they stop working. What he finds could one day help us better engineer T cells to overcome those immunosuppressive forces.
Since 2009, Swim Across America has contributed more than $5.3 million for cancer research at Fred Hutchinson Cancer Center. Funds raised by the event and by the motivated swimmers who participate enable early-career investigators to pursue groundbreaking research that can improve care for patients in Seattle and beyond. Investigators who received funding in previous years continue to build on research made possible by Swim Across America to advance understanding of breast cancer, lymphoma, pancreatic cancer, and sarcoma. We are delighted to provide this year’s update on the projects you’ve supported below. Don’t forget to register for this year’s Swim Across America – Seattle!
Dr. Meghan Flanagan
Meghan R. Flanagan, MD, MPH | Breast Cancer
Physician and affiliate investigator, Fred Hutch; Assistant professor of Surgery, UW Medicine
Project: Association of HSD3B1 (1245C) genotype with recurrence among post-menopausal women with estrogen receptor-positive, HER2- negative breast cancer
Background: Anti-estrogen endocrine therapy reduces the risk of recurrence and improves breast cancer mortality among individuals with hormone-receptor positive breast cancer. However, approximately one-quarter of patients are inherently resistant or develop resistance to endocrine therapy. Ultimately, this research may allow us to identify people with innate endocrine resistance and develop novel therapeutics and treatment strategies.
Progress statement 2022: Swim Across America’s initial support helped our team evaluate whether there is an association between a common single nucleotide variation in a gene called HSD3B1 (which is involved in hormone biosynthesis) and breast cancer outcomes. Using an extensive collection of clinical and pathologic data about patients and their tumors, we demonstrated that patients with two copies of the variant in the HSD3B1 gene had a five-fold increased risk of developing metastatic breast cancer, compared to people who did not have this variant.
In July 2022, we published findings from Swim Across America-supported research in the Annals of Surgical Oncology. Based on these results, our team received funding to study whether inheriting two copies of the variant HSD3B1 gene — which occurs in 10% to 15% of patients with estrogen receptor-positive, post-menopausal breast cancer — decreases the effectiveness of anti-estrogen medications, which are used universally in this population. Our results could indicate the need for alternative treatment strategies for these patients.
2023 update: 33 of 60 patients have completed the study, and frozen tissue from 25 patients has been analyzed for estrogen and androgen concentrations. Although only two patients had two copies of the variant HSD3B1 gene, and we do not have enough information to make conclusions about the variant versus wild-type gene, it is likely that our analysis will be the most comprehensive steroid profiling of normal and tumor breast tissue. We are also in the process of finalizing data for our primary study outcomes and anticipate this will be completed in the late spring.
Dr. Sita Kugel
Sita Kugel, PhD | Pancreatic Cancer
Assistant professor, Fred Hutch
Project: Exploring novel functions of HMGA2 in pancreatic cancer
Background: Pancreatic ductal adenocarcinoma (PDA) is an extremely lethal disease with an overall five-year survival rate of 12%. Recent work has led to the discovery that PDA can be subdivided into two principal subtypes based on transcriptional signatures: classical and basal. The basal subtype is more aggressive and leads to the worst overall survival. Our laboratory has been focused on understanding the mechanisms that drive each subtype with the aim of identifying therapeutic vulnerabilities that may be exploited in the clinic.
Progress statement 2022: Within an already challenging malignancy, certain transcriptional subtypes of pancreatic ductal adenocarcinoma are especially lethal. Funding from Swim Across America is helping us understand what defines each subtype, as well as their susceptibilities and mechanisms of resistance, to help to identify potential new treatment options for this devastating disease. Our team has recreated the classical and basal subtypes in the lab and managed to explore the differences between the two, including how they acquire resistance to first-line therapies. Our work will lay the groundwork for more targeted treatments for PDAs that can also account for their respective escape mechanisms, thereby improving outcomes.
2023 update: Some of our recent work showed that basal pancreatic tumors are sensitive to cyclin-dependent kinase (CDK) inhibitors. Our team is trialing these CDK inhibitors in patients who are also receiving standard-of-care treatment, while also looking at whether a different treatment combination affects one tumor subtype more than the other.
Simultaneously, we are using pancreatic tumor tissue taken from patients and grown in mice to test new treatment strategies in an environment similar to the human body.
Dr. Jonathan Sham
Jonathan Sham, MD, MBEE | Pancreatic Cancer
Surgical oncologist and assistant professor, Fred Hutch and UW Medicine
Project: Novel drug-eluting biopolymer to reduce pancreatic fistula and improve outcomes after pancreatic surgery
Background: Pancreatectomy, or removal of the pancreas, is the mainstay of any potentially curative treatment regimen for pancreatic cancer. Despite an overall improvement in the safety of pancreatic surgery over the past several decades, the morbidity of pancreatectomy remains exceedingly high. The most significant complication after pancreatic surgery is postoperative pancreatic fistula (POPF), which occurs in up to 50% of cases. The use of a biopolymer, poly(N-isopropylacrylamide) (PNIPAM), is an innovative approach to prevent leakage of pancreatic juice from the cut surface of the gland, while drug-eluting microspheres aims to simultaneously reduce baseline pancreatic fluid secretion. This novel dual-action approach will be tested in a validated rat model of POPF with the goal of rapid clinical translation and patient benefit.
Progress statement 2022: Swim Across America is advancing our work to improve outcomes after pancreatic surgery. Your support is enabling a trailblazing collaboration between surgeons and bioengineers to develop novel ways to stop leaks after pancreas surgery and help patients live healthier and longer lives. We have also expanded our team and published our groundbreaking research, including our development of a preclinical model for studying POPF. We continue to move this work closer to helping patients with pancreatic cancer.
2023 update: We are continuing to optimize biopolymer performance and handling characteristics for use during surgery. We are also including a chemical approach that clams use to adhere to underwater rocks in order to maximize adhesion on wet surfaces during surgery.
Dr. Jordan Gauthier
Jordan Gauthier, MD, MsC | Lymphoma
Physician and assistant professor, Fred Hutch and UW Medicine
Project: Factors associated with failure of CD19 CAR T cells in diffuse large B-cell lymphoma
Background: We are investigating two factors — T-cell dysfunction during manufacturing and the suppressive tumor microenvironment — that may play a critical role in the failure of CD19-targeting chimeric antigen receptor (CAR) T-cell therapy for people with diffuse large B-cell lymphoma (DLBCL). We are also working to identify potential targets to improve outcomes of CAR T-cell therapy for patients with DLBCL.
Progress statement 2022: The Swim Across America grant allowed us to explore two parallel questions. First, to understand whether exhausted T cells are associated with treatment failure after CAR T-cell therapy for patients with DLBCL, we analyzed blood samples from 34 patients treated on a clinical trial. While we did not confirm an association between exhausted T cells and treatment failure, we found that a higher proportion of terminally differentiated T cells may have an adverse impact on the outcomes of CAR T-cell therapy. Second, to determine if an exhausted gene signature in T cells from lymphoma tumors is associated with treatment failure, we analyzed pre-treatment tumor biopsies from 17 patients receiving CAR T-cell therapy. In patients who had a complete response to CAR T-cell therapy, we found that T-cell-associated genes were overexpressed compared to patients not in complete response after treatment. Our results suggest that tumors more susceptible to T-cell infiltration might respond better to CAR T-cell therapy.
Funds from Swim Across America also supported the development of two cutting-edge approaches, CITE-seq and CODEX, that allow us to study proteins and DNA from single cells and take 3D photographs of biopsies before and after therapy. These tools will help us better understand why CAR T-cell therapy does not work in some patients. Identifying why treatment fails at a single-cell level will have a dramatic impact on how we design the next generation of CAR T-cell therapies.
2023 update: Using tools we developed with the support of Swim Across America, we are now able to specifically study how CAR T cells “talk” to other cells inside lymphoma tumors. We are also now using CITE-seq to analyze 20 tumor biopsy samples from patients undergoing CAR T-cell therapy in clinical trials. We are looking at associations between specific immune cell populations and outcomes, such as anti-cancer effects and toxicity.
Dr. John Lee
John K. Lee, MD, PhD | Sarcoma
Previously physician and assistant professor, Fred Hutch and UW Medicine; currently at UCLA
Project: Development of STEAP1 chimeric antigen receptor T-cell therapy for Ewing sarcoma
Background: Approximately 200 adolescents and young adults in the U.S. are diagnosed each year with Ewing sarcoma, a cancer of the soft tissue and bone. When Ewing sarcoma spreads, patients face a very grim prognosis, as no available treatments eradicate the disease. If successful, our studies will help lay the groundwork for the development and clinical translation of a first-in-field CAR T-cell immunotherapy for Ewing sarcoma that targets the protein STEAP1.
Progress statement 2022: Swim Across America funding helped us evaluate whether a novel CAR T-cell therapy targeting the protein STEAP1 could be an effective strategy to treat patients with Ewing sarcoma. Our results indicate that human Ewing sarcoma tumor models commonly express STEAP1 and are susceptible to killing by STEAP1 CAR T cells. In related studies, we have also determined that STEAP1 CAR T-cell therapy appears safe in a novel mouse model that we engineered to express human STEAP1. We have seen highly promising activity in multiple preclinical models of Ewing sarcoma, and we licensed the technology to a company for clinical development.
2023 update: The Swim Across America grant enabled studies, now complete, confirming the anti-cancer activity of STEAP1 CAR T-cell therapy in preclinical models of Ewing sarcoma. A clinical trial in humans at Fred Hutch and Seattle Children’s Hospital is now being planned.
To date, Swim Across America has contributed close to $4.2 million for clinical research at Seattle Cancer Care Alliance and Fred Hutch. Starting in 2019, funds raised from the SAA-Seattle have gone to support breakthrough research by young investigators. In 2021, six grants were awarded to researchers focused on: lymphoma, sarcoma, breast, pancreatic, and urological cancer research. Below, the grant recipients share progress statements on their research over the last year.
Dr. Meghan Flanagan
Dr. Meghan Flanagan Research focus: Breast cancer Project title: Association of HSD3B1 (1245C) genotype with recurrence among post-menopausal women with estrogen receptor- positive, HER2- negative breast cancer Background: Endocrine (antiestrogen) therapy reduces the risk of recurrence and improves mortality among women with hormone-receptor positive breast cancer. However, approximately one-quarter of women are inherently resistant or develop resistance to endocrine therapy. Ultimately, this research may allow us to identify women with innate endocrine resistance and develop novel therapeutics and treatment strategies. Progress Statement: The SAA funds were used to evaluate whether an association exists between a mutation in a gene (HSD3B1, involved in hormone biosynthesis) and breast cancer outcomes. Using extensively collected clinical and pathologic data about patient demographics, tumor and treatment data and recurrence rates, we were able to show that women with two mutations in the HSD3B1 gene had higher rates of distant metastatic recurrence compared to those women who did not have this mutation. Future studies will be forthcoming to determine how this mutation may decrease the effectiveness of anti-estrogen medications that are used universally in post-menopausal ER+ breast cancer. This mutation is found in up to 15 percent of ER+ post-menopausal breast cancer patients, and if shown to decrease the effectiveness of anti-estrogen medications, there would be potential indications for alternative treatment strategies in these patients.
Dr. Sita Kugel
Dr. Sita Kugel Research focus: Pancreatic Cancer Project title: Exploring novel functions of HMGA2 in pancreatic cancer Background: Pancreatic Ductal Adenocarcinoma (PDA) is an extremely lethal disease with a 5-year survival rate of less than 10%. Recent work has led to the discovery that PDA can be subdivided into two principal subtypes based on transcriptional signatures: classical and quasi-mesenchymal (QM). The QM PDA subtype is more aggressive and has the worst overall survival. Our laboratory has been focused on understanding of the mechanisms that drive each subtype in hopes of identifying therapeutic vulnerabilities that may be exploited in the clinic. Progress Statement: Within an already challenging malignancy, there are transcriptional subtypes of pancreatic ductal adenocarcinoma that are especially lethal. Understanding what defines each subtype, as well as their susceptibilities and mechanisms of resistance, will help to identify new targeted therapies or combination therapies and lead to more treatment options for this devastating disease.
Dr. Jonathan Sham
Dr. Jonathan Sham Research focus: Pancreatic Cancer Project title: Novel Drug- eluting Biopolymer to Reduce Pancreatic Fistula and Improve Outcomes After Pancreatic Surgery Background: Pancreatectomy is the mainstay of any potentially curative treatment regimen for pancreatic cancer. Despite an overall improvement in the safety of pancreatic surgery over the past several decades, the morbidity of pancreatectomy remains exceedingly high. The most significant complication after pancreatic surgery is postoperative pancreatic fistula (POPF), which occurs in up to 60% of cases. The use of a biopolymer, poly(Nisopropylacrylamide) (PNIPAM), is an innovative method to prevent leakage of pancreatic juice from the cut surface of the gland, while the suspended octreotide- eluting microspheres will simultaneously reduce baseline pancreatic fluid secretion. This novel dual-action approach will be tested in a validated rat model of POPF with the goal of rapid clinical translation and patient benefit. Progress Statement: Swim Across America is advancing our work to improve outcomes after pancreatic surgery. Their support is enabling a trailblazing collaboration between surgeons and bioengineers to develop novel ways to stop leaks after pancreas surgery and make patients live happier, healthier and longer lives. Polymer synthesis is moving forward, and two teams are working on creating and testing polymers with different characteristics for use in our animal experiments.
Dr. Jordan Gauthier
Dr. Jordan Gauthier Research focus: CAR T-cell therapy Project title: Factors associated with failure of CD19 CAR T cells in diffuse large B cell lymphoma Background: We are investigating two factors potentially critical to failure of CD19 CAR T-cell therapy for DLBCL: a) T cell dysfunction, impeding the generation of functional CAR T cells during manufacturing; b) the suppressive tumor microenvironment (TME). Our studies will better characterize T cell dysfunction and the TME as core mechanisms of failure of CD19 CAR T cells and identify potential targets to improve outcomes of CAR T-cell therapy for DLBCL. Progress Statement: The Swim Across America grant allowed us to explore the two following aims. Aim 1: To determine whether exhausted T cells are associated with treatment failure after CAR T-cell therapy for diffuse large B-cell lymphoma (DLBCL). We analyzed blood samples from 34 DLBCL patients treated on a clinical trial of CAR T-cell therapy. While we did not confirm an association between exhausted T cells and treatment failure, we found that a higher proportion of terminally differentiated T cells may have an adverse impact on the outcomes of CAR T-cell therapy. Aim 2: To determine if an exhausted gene signature in T cells from lymphoma tumors is associated with treatment failure, we analyzed pre-treatment tumor biopsies obtained from 17 patients receiving CAR T-cell therapy. In biopsies from patients in complete response after CAR T-cell therapy, we found that T cell-associated genes were overexpressed compared to patients not in complete response after treatment. This suggests that tumors more permissive to T cell infiltration might respond better to CAR T-cell therapy. So far, we have not confirmed that an exhausted gene signature is associated with treatment failure. The SAA grant has been used to design and optimize novel assays that will allow us to further address this aim in the future.
Dr. John Lee
Dr. John Lee Research focus:Sarcoma Project title: Development of STEAP1 chimeric antigen receptor T-cell therapy for Ewing sarcoma Background: Ewing sarcoma (ES) is a soft tissue/bone cancer with 200 newly diagnosed adolescents/young adults per year in the United States. Patients with metastatic dissemination face a very grim prognosis as available treatments are unable to eradicate the disease. New therapeutic approaches are needed. If successful, these studies will help lay the groundwork for the development and clinical translation of a first-in-field STEAP1 CAR T-cell immunotherapy for ES. Progress Statement: We applied the Swim Across America grant to evaluate whether a novel chimeric antigen receptor (CAR) T cell therapy targeting the protein STEAP1 could be an effective strategy to treat Ewing sarcoma. Our results indicate that human Ewing sarcoma tumor models commonly express STEAP1 and are susceptible to killing by STEAP1 CAR T cells. In related studies, we have also determined that STEAP1 CAR T cell therapy appears safe in a novel mouse model that we engineered to express human STEAP1. Together, these findings provide the rational to translate STEAP1 CAR T cell therapy into clinical trials for Ewing sarcoma in the near future.
Dr. Adam Gadzinski
Dr. Adam Gadzinski Research focus:Urological cancer Project title: Interstate Telehealth to improve access to urological cancer care among rural patients. Background: Timely access to urological cancer care is challenging for rural patients who often travel great distances to tertiary centers. This is particularly true for patients residing in the WWAMI (Washington, Wyoming, Alaska, Montana, Idaho) region. We hypothesize that Telehealth will provide similar patient satisfaction, reduced costs, and earlier time to treatment. We further hypothesize that implementation of the interstate Telehealth program will decrease referral to visit time and increase clinical efficiency. Lastly, we hypothesize that providing Telehealth appointments will increase the frequency of referrals from rural areas. We anticipate that implementation of our interstate Telehealth program will improve access to urological cancer care for rural and underserved patients throughout the WWAMI region. Progress Statement: Our SAA grant has been used to support our telemedicine research efforts to assess the quality of telemedicine visits for cancer patients from rural areas and the Pacific Northwest states. We have demonstrated that telemedicine visits save cancer patients and their families a significant amount of time and money that would have been spent traveling to doctor appointments. We also found that patients are very satisfied with receiving cancer care remotely via telemedicine, especially during the COVID-19 pandemic.
With the support of Swim Across America grant funding, researchers at Rush University Medical Center are gaining momentum in their quest to discover the early detection tools and treatment options of the future in the fight against cancer. RUSH’s experts intimately understand the physical, emotional and financial burdens of cancer on patients’ lives, and they refuse to let the disease rest as the second leading cause of death in the U.S. Since 2012, Swim Across America–Chicago has awarded More than $2M that has funded these early stage research projects.
Dr. Carl Maki
Grant Recipient: Carl Maki, PhD Professor in the Department of Anatomy & Cell Biology at Rush Medical College
Project: Targeting proteins to improve drug responses for patients with treatment-resistant breast and lung cancers
Project Details: By studying cancer at the molecular level, Maki and his team have made significant strides in identifying promising new options for treatment-resistant breast and lung cancers.
In 2015 Maki received an SAA grant to study a family of enzymes known as prolyl peptidases (which regulate blood pressure and appetite) as a possible mechanism to help prevent or alleviate resistance to the drug tamoxifen, one of the most widely used therapies for the 80% of women with breast cancer whose tumors are considered estrogen receptor-positive. Maki and his team found that an enzyme inhibitor for prolyl peptidases, used in conjunction with tamoxifen, effectively killed breast cancer cells in rodents. Using these promising findings, Maki applied for and received a prestigious R01 research award for continued study from the National Institutes of Health and a grant from the Department of Defense to extend this research into triple-negative breast cancer.
In 2020 Maki was awarded another SAA grant to study proteins called histone demethylases in non-small cell lung cancer. Among the deadliest of all cancers, this accounts for about 4 in 5 lung cancer cases. Maki and his colleagues are studying how these proteins may allow lung cancer cells to resist the drugs currently used to treat the disease. By blocking these proteins, the team has been able to kill lung cancer cells in laboratory studies and lung tumors in mice. They identified a novel mechanism for how these inhibitors improve treatment outcomes and recently published their results.
“What starts out as an idea might result in something great,” Maki said. “SAA gives less established researchers a chance and helps all researchers fund pilot projects that ultimately can lead to bigger things.”
Dr. Animesh Barua
Grant Recipient: Animesh Barua, PhD Associate Professor in the Department of Anatomy & Cell Biology at Rush Medical College Director of the Proteomics Core and MicroRNA and Gene Expression Core
Project: Seeking an improved early detection test for ovarian cancer
Project Details: Throughout his career, Barua has relentlessly pursued the development of an effective early detection test for ovarian cancer. With an SAA grant received in 2020, he and his team are drawing upon extensive experience with immunoassays and ultrasound imaging of ovarian tumors to take the next steps forward in this important area of research. In this study, Barua’s lab is developing a fresh approach to early detection testing involving the fimbriae (fingerlike protein branches that guide an egg during ovulation) of the fallopian tubes. Emerging information shows that high-grade serous carcinoma — the most malignant and most common type of ovarian cancer — originates from the fimbriae. The aims of Barua’s study include identifying specific protein markers associated with cancer development in the fimbriae and determining the efficacy of these markers in predicting cancer growth.
Dr. Amanda Marzo
Grant Recipient: Amanda Marzo, PhD Assistant Professor in the Department of Internal Medicine, Division of Hematology, Oncology and Cell Therapy at Rush Medical College
Project: Bolstering the body’s natural immune response for greater success in the battle against breast cancer
Project Details: Tumor-infiltrating CD8 T-cells are essential for tumor immunity. However, many of these cells become exhausted and are unable to protect against tumor growth. Key molecules known as checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1) expressed on tumor cells and programmed cell death protein 1 (PD-1) expressed on CD8 T-cells, have been shown to be a hallmark of CD8 T-cell exhaustion. For most tumors, blocking PD-1/PD-L1 signaling does not result in tumor rejection. A main cause for the ineffectiveness of checkpoint blockade immunotherapy lies in the dysfunctional state of CD8 T-cells once they enter the tumor. CD8 T-cells are specialized in killing tumor cells but face multiple suppressive signals that dampen their ability to effectively respond. Using an SAA grant received in 2019,Marzo and her colleagues seek to improve scientists’ understanding of how other immune-modulating treatments can improve CD8 T-cell responsiveness to checkpoint inhibitors. Specifically, the researchers aim to determine if metformin, an anti-diabetic drug, could enhance tumor-infiltrating CD8 T-cell responsiveness to PD-1 blockade therapy by altering breast cancer metabolism. The team also seeks to establish if bolstering the number of infiltrating CD8 T-cells into the tumor using interleukin-15 complexes (known to cause proliferation of cells and increase their killing ability) in combination with PD-1 blockade therapy could induce regression of established breast tumors and lead to long-term tumor immunity. Marzo and her team plan to publish the results of their study and are using preliminary data generated from this research to apply for a federal R21 grant.
Dr. Alan Blank
Grant Recipients: Alan T. Blank, MD, MS Assistant Professor in the Department of Orthopedic Surgery, Section of Orthopedic Oncology at Rush Medical College
Jitesh Pratap, PhD Associate Professor in the Department of Anatomy & Cell Biology at Rush Medical College
Dr. Jitesh Pratap
Project: Pursuing therapeutic approaches to prevent breast cancers from
metastasizing to the bones
Project Details: In this study funded by a 2019 SAA grant, Blank and Pratap seek to fulfill a need for the development of a therapy that can prevent primary breast cancers from metastasizing to the bones and surviving there. The researchers hypothesize, based on results of previous studies, that a subgroup of patients with breast cancer that has metastasized to the bone has high levels of autophagy (a process of recycling of cellular components), Runx2 proteins and acetylated α-tubulin — worsening their chances of survival. To investigate this, the researchers are working to determine the clinicopathologic association with the autophagy pathway in tumor samples from patients with cancer that has metastasized to the bone. They are also creating patient-derived xenograft models of bone metastasis. Blank and Pratap hope the results of this study will propel the development of better combinatorial therapeutic approaches to treat bone metastasis.
Dr. Faraz Bishehsari
Grant Recipient: Faraz Bishehsari, MD, PhD Associate Professor of Medicine & the Graduate College in the Department of Internal Medicine, Division of Digestive Diseases and Nutrition, Section of Gastroenterology at Rush Medical College Associate Director for Molecular & Translational Research for the Rush Center for Integrated Microbiome & Chronobiology Research
Project: Pursuing precision medicine to improve outcomes for pancreatic cancer patients
Project Details: Patients with pancreatic ductal adenocarcinoma — the most common form of pancreatic cancer — face poor survival rates, with only 6%-8% of patients surviving five years after diagnosis. This cancer does not respond well to targeted therapies. Bishehsari and his colleagues received an SAA grant in 2019 to establish a platform towards precision medicine in order to tailor therapies based on patients’ individual tumor characteristics. The researchers have developed primary cancer cells from a small tissue sample obtained during diagnostic pancreatic biopsies from pancreatic ductal adenocarcinomas. Molecular profiling of these patient-derived tumor organoids explained the variation in response to a variety of conventional and investigational therapies. They are optimizing this platform to help eventually establish individualized treatments for pancreatic cancer patients.
Dr. Jeff Borgia
Grant Recipient: Jeffrey A. Borgia, PhD Associate Professor in the Department of Anatomy & Cell Biology at Rush Medical College Director of the Rush University Cancer Center Biorepository and Rush Biomarker Development Core
Project: Identifying biomarkers for the improved evaluation and treatment of stage I non-small cell lung cancer
Project Details: Lung cancer is the leading cause of cancer-related mortality in the United States, but evidence is surfacing that widespread lung cancer screening programs may improve patient outcomes when the disease is detected early. Borgia and his team received an SAA grant in 2020 to develop a new diagnostic method to improve physicians’ ability to predict the recurrence of stage I non-small cell lung cancer, or NSCLC. This would help physicians identify patients who would benefit from adjuvant treatment options or closer surveillance. The aims of this study include identifying biomarkers for disease recurrence in stage I NSCLC patients and evaluating these biomarkers for their value in predicting recurrence.
Swim Across America has supported cancer research at Rush University Medical Center since 2012 through more than $2 million in grant funding. Together, Swim Across America and RUSH are relentlessly fighting cancer, working to save lives.
Picture a sunny and warm mid-August morning in Colorado. Retired Olympians such as Missy Franklin and George DiCarlo are smiling with water enthusiasts of all ages and abilities. They enter the water of Chatfield Reservoir in Littleton to “Make Waves to Fight Cancer” with the Swim Across America-Denver charity swim. There’s a sense of community as supporters and family cheer for them. Not because they’ll be racing for first place, rather because they’re all there to raise money that will provide grants for pediatric cancer at Children’s Hospital Colorado.
Created in 2018, Swim Across America-Denver has granted $545,917 to research projects at the Center for Cancer and Blood Disorders at Children’s Colorado. Uniquely, all the proceeds from Swim Across America-Denver stay in our community to fund research projects at Children’s Colorado where philanthropic grants from Swim Across America are necessary to make progress in giving hope to kids and their families who are fighting cancer. Here are the projects that are being funded by SAA:
The acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) research project, led by Drs. Amanda Winters, Taizo Nakano, and Craig Forester, aimed at bringing new therapies into phase II of clinical trials for pediatric MDS and AML to better define how to diagnose, classify and treat MDS patients.
The tumor research project, led by Dr. Adam Green, which will characterize the immune response to new brain tumors to better establish which types are amenable to cancer immunotherapy and provide a new prognostic marker for these diseases.
The sepsis biomarker project, led by Dr. Leonora Slatnick, will lead to novel ways of diagnosing and managing infectious complications in immunosuppressed patients.
The CAR-T Cell project, led by Dr. Lindsey Murphy and collaborating with Dr. Winters and members of the BMT-Cellular Therapeutics team, aims to use novel laboratory methods for detecting CAR-T cells in patients receiving those therapies to better understand how patients respond to these therapies and improve cure rates.
“With [Swim Across America grants] we’re building the largest national database on pediatric myelodysplastic syndrome (MDS) to collect data on all of the past and future children with this life-threatening disorder. SAA’s contribution will help encourage research collaboration at over 50 children’s hospitals to enter data that will help develop a national standards-of-practice to treat pediatric MDS,” said Taizo Nakano, MD.
Grants from SAA will also be used to fund site initiation of a nationwide clinical trial for pediatric MDS at Children’s Colorado and will also be critical for Dr. Forester and Dr. Winters as they investigate the biological activity of the drug combination being tested.
“This will allow us to understand why the drugs work for pediatric MDS and perhaps enable us to predict at diagnosis which children with MDS are more or less likely to benefit from these drugs,” said Amanda Winters, MD.
“We welcome and invite our Colorado community to join us,” said Nicole Vanderpoel and Jessica Vitcenda, community leaders for SAA—Denver. “You can swim, volunteer or do a virtual activity with all the proceeds staying in Denver to benefit Children’s Colorado.”
Swim Across America is proud to share that MUSC Hollings Cancer Center researcher Haizhen (Jen) Wang, Ph.D., has been awarded a five-year $344,000 per year grant by the National Cancer Institute (NCI) to pursue her early investigator studies in leukemia. Prior to receiving NCI funding, Dr. Wang’s research was supported by $65,000 in grants from the Swim Across America – Charleston-Kiawah charity swim held annually at Kiawah Island Golf Resort.
Swim Across America helps fill the funding void by providing grants so doctors can conduct clinical trials and research that can lead to breakthroughs in detection and treatment. When this funding leads to larger grants like Dr. Wang’s with the NCI, it’s a win not only for future patients but for all Swim Across America participants, donors and beneficiary partners.
According to the Hollings website, Dr. Wang’s research “focuses on uncovering the connection between cancer metabolism and cancer immunology. Her research has shown that a molecule called cyclin-dependent kinase 6 (CDK6) may be a key regulatory molecule in cancers such as leukemia.” The grant funding has already started this year and allows Dr. Wang to add research team members. The grant also has the unique option to extend two more years.
SAA-Charleston-Kiawah has supported MUSC Hollings Cancer Center since 2019 and has welcomed Dr. Wang, her family and other members of the Hollings team to participate in our annual charity swim.
Swim Across America – San Francisco Event Director and cancer survivor Susan Helmrich will be interviewing “Why We Swim” author Bonnie Tsui in a Zoom Conversation this Wednesday, June 3rd. Topics will include all things swimming, community and the reasons “why we swim.” Susan Helmrich has been the Event Director for SAA – San Francisco for 13 years and her “Team Susan Survives” is consistently a top national fundraising team for Swim Across America.
“Susan has been a member of U.S. Masters Swimmers for decades and a daily swimmer for most of her life — except during her three bouts with cancer. An epidemiologist, she has studied how over-the-counter and prescription medications affect women’s health and the effects of physical activity on health and well-being” says Berkeley City Club, the host of the virtual conversation.
Both women are avid swimmers and excited to talk about what draws them to the water and what they love about swimming. The Zoom Conversation will take place on Wednesday, June 3rd at 7:00 p.m. PST (10:00 p.m. EST). Swimmers and non-swimmers alike are invited to participate. RSVP here: sydneyc@swimacrossamerica.org.
Swim Across America is finding ways to continuing supporting local beneficiaries during this challenging time. Local leadership has been donating meals to selfless healthcare workers at our beneficiary institutions as they continue putting themselves at risk to serve and protect all of us during this crisis. Our unwavering commitment to support our beneficiaries remains, and now more than ever we stand by each of them.
SAA – Houston
MD Anderson Cancer Center
Swim Across America – Houston treated the Pediatric and Brain & Spine Teams at MD Anderson Cancer Center to lunch as a way to express their sincerest appreciation for their service.
SAA – Dallas
Innovative Clinical Trials Center – Baylor Scott & White Health
A big thumbs up from Dr. Becerra after the Swim Across America – Dallas team brought “Taco Tuesday” to the staff of the Swim Across America Innovative Clinical Trials Center at Baylor Scott & White Health.
SAA – San Francisco Bay
UCSF Benioff Children’s Hospitals
SAA – San Francisco Bay provided their beneficiary and partners UCSF Benioff Children’s Hospitals with a nutritious breakfast last week to thank them for their continued efforts in supporting the Survivors of Childhood Cancer Program. Thanks to our friends Checkers Catering & Special Events for providing the scrumptious breakfast to these Capeless Heroes!!
SAA – Atlanta
Children’s Healthcare of Atlanta
Swim Across America – Atlanta had Chick-Fil-A cookies dropped off for the past and present medical staff who have been funded by Swim Across America to show our appreciation for all of their hard work. They returned the love with some fun photos with their cookies.
SAA – Long Island Sound
NY Presbyterian Hospital &
Memorial Sloan Kettering Cancer Center
Swim Across America – Long Island Sound has been busy reaching out to their beneficiaries and scheduling these meal drop-offs. The SAA – LIS team brought breakfast to the nurses at the front line in the Urgent Care Unit at Memorial Sloan Kettering. They also provided lunch to the ICU team at NY Presbyterian Hospital.
A huge thank you to all healthcare workers for your courage and unselfish commitment to patients and the communities you serve!
Speedo USA and Swim Across America have teamed up to donate 2,000 goggles to Swim Across America hospital beneficiaries. The goggles are offered as protective eyewear to hospital medical staff.
“Our hospital partners shared a need for protective eyewear so we reached out to Speedo USA to see if they might be able to help,” commented Rob Butcher, Swim Across America CEO.
Swim Across America-Dallas team captain Alan Wright of Baylor Oncology shows off his SAA spirit.
“Many of Speedo’s athletes support Swim Across America so when we were approached with the need and that we could help, we were delighted to do so,” shared Andy Long, CEO of Pentland Brands.
Swim Across America hosts charity swims with the proceeds funding cancer research. If you feel inspired, you may donate to Swim Across America through this link.
Swim Across America 