Dr Aude Chapuis is an oncologist who sees patients in the Bone Marrow Transplant and Immunotherapy services. She leads a laboratory employing a translational pipeline to improve T cell receptor (TCR) gene-engineered immunotherapy. Their work spans target identification, generation of high-affinity TCR constructs and standard operating methods to translate these constructs into effective cell products for patients, clinical trial development and initiation, and sophisticated high dimensional immune-monitoring to maximize the information that can be derived from each treated patient. Current projects include T cell therapies against virally-driven tumors (targeting Merkel-cell polyoma virus antigens in Merkel cell carcinoma), solid tumors (targeting the MAGE-A1 cancer-testis antigen in non-small cell lung cancer, triple negative breast cancer, and bladder cancers; and targeting WT1 antigen in thoracic and gynecological cancers), and leukemias (targeting two WT1 epitopes in acute myeloid leukemia). The lab benefits from a highly collaborative network at the Fred Hutch, including expert investigators in basic science, cancer immunology and immunotherapy, as well as disease-specific clinical oncologists.
Lahman MC, Schmitt TM, Paulson KG, Vigneron N, Buenrostro D, Wagener FD, Voillet V, Martin L, Gottardo R, Bielas J, McElrath JM, Stirewalt DL, Pogosova-Agadjanyan EL, Yeung CC, Pierce RH, Egan DN, Bar M, Hendrie PC, Kinsella S, Vakil A, Butler J, Chaffee M, Linton J, McAfee MS, Hunter DS, Bleakley M, Rongvaux A, Van den Eynde BJ, Chapuis AG, Greenberg PD. Targeting an alternate Wilms' tumor antigen 1 peptide bypasses immunoproteasome dependency.
Chapuis AG, Egan DN, Schmitt TM, McAfee MS, Paulson KG, Voillet V, Gorttardo R, Ragnarsson GB, Bleakley M, Yeung CC, Mulhauser P, Nguyen HN, Kropp LA, Castelli L, Wagener F, Hunter D, Lindberg M, Cohen K, Seese A, McElrath J, Duerkopp N, Gooley TA, Greenberg PD. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Paulson KG, Voillet V, McAfee MS, Hunter DS, Wagener FD, Perdicchio M, Valente WJ, Koelle SJ, Church CD, Vandeven N, Thomas H, Colunga AG, Iyer JG, Yee C, Kulikauskas R, Koelle DM, Pierce RH, Bielas JH, Greenberg PD, Bhatia S, Gottardo R, Nghiem P, Chapuis AG. Acquired cancer resistance to combination immunotherapy from transcriptional loss of class I HLA.
Investigators in The Program in Immunology are learning how immune cells respond to disease and how to safely enhance immune responses to better control, cure and potentially prevent cancers and other serious diseases. Nobel Prize-winning work on bone marrow transplantation began in the 1960s at the Fred Hutch, and provided the first definitive example of the immune system’s curative power. Fred Hutch researchers went on to show that donor immune T cells play a major role in successful transplant outcomes. In the 1990s, Program in Immunology investigators proved that antigen-specific T cells can be isolated, expanded in the laboratory and adoptively transferred to patients to augment T cell immunity. Techniques have since been developed to genetically engineer T cells to enhance their survival and their anti-cancer activities. And, studies are now showing how to use other types of immune cells to boost therapeutic immune responses. With our depth and breadth of expertise, we are advancing a detailed understanding of immunological processes and developing revolutionary immunotherapies to fight disease.