Research Projects / Team Leaders

Program in Immunology

Research Projects

Lab technicians process therapeutic T cells.

Photo by Robert Hood / Fred Hutch News Service

Our team members are leading clinical trials in which optimized T cells are produced, expanded and infused into patients to treat otherwise life-threatening viral infections. Selected T cells have also been developed to prevent the “graft-versus-host disease” that happens when bulk T cells attack healthy tissues, significantly reducing the life-saving potential of hematopoietic stem cell transplantation. Other clinical trials are using immune T cells to treat patients with cancers, including melanoma, sarcoma, lymphoma and leukemia, as well as breast and lung cancers.

State-of-the-art laboratory techniques, most developed Fred Hutch, are used to monitor the infused T cells and learn how the T cell therapies can be further improved, including by combining multiple immunotherapy approaches. New T cell therapies are being designed and advances are likely to help many more patients in the near future.

Team Leaders

Dr. Bleakley is a pediatric oncologist specializing in hematopoietic stem cell transplantation and the treatment of leukemia relapse. Her active research is focused on the development of new transplantation strategies and immunotherapies to improve outcomes for patients of all ages who are diagnosed with high-risk leukemia. Her ongoing research includes: 1) development and evaluation of strategies to engineer T cell grafts to prevent dangerous side-effects and enhance anti-cancer activity after transplantation, 2) development of adoptive T cell therapy to prevent/treat relapse after allogeneic transplantation and 3) discovery of leukemia-associated “minor histocompatibility” antigens as targets for future immunotherapy, graft engineering and/or vaccination to manage leukemic relapse post-transplant.

Dr. Chapuis is an expert in hematopoietic stem cell transplantation and adoptive T cell therapies for patients with life-threatening viral infections and various malignancies, including solid tumors. Her research is focused on improving the utility of both native and gene-modified antigen-specific T cells by qualifying specific tumor antigens as valid T-cell targets and producing high-quality TCRs for T cell engineering. Her ongoing studies aim to 1) improve the survival and antitumor activity of adoptively transferred T cells and 2) modulate the recipient immune environment to assure optimal therapeutic T cell activity. Clinical trials and correlative laboratory studies are underway for patients with myeloid leukemia and patients with polyoma virus-associated Merkel cell carcinoma.

Dr. Dudakov’s expertise is in immunology and regenerative medicine, especially in immune tissue regeneration after various forms of injury. His primary focus is the thymus, critical to a healthy immune system’s ability to fight diseases, including cancer. He is working to clarify the biological processes triggered in the thymus by normal aging and by acute damage such as by certain autoimmune diseases, the radiation and drug treatments that cancer patients receive and the graft-versus-host disease that some patients suffer after hematopoietic stem cell transplantation. By elucidating how the thymus can restore immune function, new therapies might be developed to enhance T-cell immunity, as needed. His work has already identified a secreted protein (cytokine) known as interleukin-22 that is involved in thymus regeneration and might be leveraged in novel, immune-boosting therapies.

Dr. Greenberg is the founding head of the Fred Hutch Program in Immunology and a world-recognized leader in the fields of T cell biology and immunotherapy. With particular expertise in target antigen discovery, Dr. Greenberg and his laboratory are using state-of-the-art cellular and molecular methods and models to develop adoptive T cell therapies for cancer patients and patients with life-threatening infections. Current studies include 1) a clinical trial of autologous, TCR-modified T cells for patients with non-small cell lung cancer, along with laboratory monitoring of immune-suppressing molecules that might be blocked in a follow-up, and 2) a clinical trial of TCR-engineered T cells for AML patients. Other ongoing studies are clarifying precisely how tumor antigens are recognized by T cells, what is required for effective T cell activation, how tumors can inactivate T cells and how the tumor microenvironment can reduce the function of T cells that reach tumor sites. Findings are being used to design molecular strategies for engineering optimally effective T cells.

Dr. Mark Headley

Dr. Headley is working to understand the biological underpinnings of metastasis, the spread of cancer cells from a primary tumor to distant organs. He and his lab are especially focused on the tumor-immune cell interactions that variably promote or defend against metastasis to the lung, one of the most common and most detrimental sites of tumor spread. They use advanced microscopy and surgical techniques, paired with high-resolution single cell profiling to directly visualize tumor cells and immune cells in live lungs in real-time and in unprecedented detail. New findings show that particular pro-tumoral immune cells (macrophages) and anti-tumoral immune cells (dendritic cells and patrolling monocytes) encounter and ingest tumor-derived particles. The Headley team seeks to understand how these interactions define anti-tumor immune responses and patient outcomes.

Dr. Pollack is an expert on cancers of the bone and soft tissues, known as sarcomas, and new therapies for sarcoma patients, including immunotherapies. His laboratory is developing new ways to enhance immune responses against these deadly cancers and learning how sarcoma cells evade therapeutic T cells so he can develop strategies to overcome these resistance mechanisms. He has already launched multiple clinical trials of novel immune-stimulating strategies including an experimental cancer vaccine. Dr. Pollack’s lab is working to 1) develop a library of high-affinity, antigen-specific TCRs for “off-the-shelf” T cell anti-sarcoma therapies, 2) validate strategies to routinely generate high-affinity, antigen-specific T cells, 3) enhance the function of sarcoma-specific T cells and 4) develop more sensitive ways to measure tumor-specific T cell responses in immunotherapies.

Dr. Riddell is a world-recognized expert in both TCR- and CAR-based immunotherapies. He led the first clinical trial of adoptively transferred T cells, to prevent dangerous viral infections after stem cell transplantation, and the first trial of leukemia-reactive T cells to prevent relapse post-transplant. His lab has developed now widely used techniques for the isolation, expansion and genetic modification of T cells, and for monitoring T cell safety, persistence and clinical activity. These state-of-the-art methods are being used with specimens from clinical trials of adoptive CD19 CAR-modified T cells, to define 1) the attributes of optimal therapeutic T cells, 2) the biologic mechanisms of tumor eradication versus escape and 3) clinical interventions that can positively modulate the function of transferred T cells. Other ongoing research is aimed at 4) discovering additional tumor target antigens and designing effective CARs for patients with blood cancers and other malignancies, including breast and lung cancers and 5) developing laboratory models to learn how to further improve adoptive immunotherapy.

Dr. Rongvaux’s studies focus on the “innate” immune response, the very earliest steps in developing disease immunity. He is especially focused on learning how dying cells affect the activation of the innate immune response and how innate immune cells help clear pathogens and tumor cells. To study the role of particular genes in these critical processes, he developed the "MISTRG" mouse model in which genes encoding immune-promoting cytokine proteins are replaced by their human versions. These human cytokines support the development and function of human immune systems in the mice, including monocytes/macrophages and natural killer (NK) cells of the innate immune system. The MISTRG model can support patient-derived immune cells, which empowers studies of the fundamental mechanisms of human immune responses and initial tests of therapies that might be used to enhance disease-fighting immunity.

Dr. Stephan is an expert in the fast-moving field of immuno-bioengineering. His laboratory designs synthetic materials to be used in novel cancer immunotherapies. The group recently developed 1) a way to embed cancer-fighting T cells in a resorbable material that can be surgically implanted into tumors or where a tumor was just excised. Mouse models show this approach can safely provide an effective treatment option for inoperable tumors and the implants are now ready to be tested in the clinic to potentially spare patients from repetitive operations, rounds of radiation or chemotherapy and extended hospital stays. The groups is also 2) using tiny “nanoparticles” to carry genes directly to patients’ T cells and thereby confer antitumor specificity without having to isolate immune cells and perform the elaborate laboratory procedures that are used today. The goal is to develop a nanoparticle repertoire such that treatment with the appropriate nanoparticle could begin immediately following diagnosis.

Dr. Turtle is an expert in hematopoietic stem cell transplantation. He leads clinical immunotherapy trials, including one CD19-targeting T cell therapy for patients with B cell lymphomas and leukemia and an ongoing clinical trial of CD19-specific CAR- T cells after allogeneic stem cell transplantation. Dr. Turtle’s laboratory has extensive expertise in the production of therapeutic T cells, and in detailed analyses of human T cells in healthy individuals and cancer patients. In particular, they are working to 1) characterize functionally distinct subsets of human T cells and learn how they impact immune reconstitution to minimize transplant-related complications and maximize successful outcomes for survivors. Dr. Turtle’s lab is also 2) uncovering the ways in which native bacteria in a patient’s gastrointestinal track affect post-transplant immune recovery and potential complications, and 3) developing new strategies to treat patients with acute myeloid leukemia using genetically modified T cells.

Dr. Warren is an expert immunologist with experience in allogeneic stem cell transplantation and immunotherapy. His laboratory studies tumor antigens and the immune responses that mediate tumor regression, aimed at developing new vaccines and other immunotherapies. Much of the lab’s current effort focuses on 1) the graft-versus-tumor effect (GVT), mediated primarily by donor-derived T cells, 2) graft-versus-host disease (GVHD), which also involves donor T cells but can cause serious complications after allogeneic transplantation, and 3) dissecting responses that a patient’s own (autologous) immune cells can make against solid cancers, identifying tumor antigens that might be targeted with T cell therapy. Dr. Warren also studies Burkitt lymphoma, the most common pediatric cancer in sub-Saharan Africa where it is usually fatal within one year, rarely affecting children in North America and Europe. The lab is actively studying the biology of this cancer, in order to develop more effective therapies.