First and for most we do this for the patients and their families. We hope that our oncology research leads to more time with the ones we love.
HOPE OF LIFE
As we take hold of immunotherapy using the immune systems powerful mechanisms to fight cancer, we also fight to bring hope with the prospect of a healthier cancer free life.
PURSUIT OF KNOWLEDGE
We are committed to engaging the never ending challenge to be on the cutting edge of science and technology that fuels our research to keep discovering.
ADOPTIVE T CELL THERAPIES TARGETING WT1
WT1 is a protein that is highly expressed in a wide variety of cancer types. Collaborating with Fred Hutch colleagues in Dr. Phil Greenberg’s group, Dr. Chapuis participated in the identification and generation of a native, high-affinity WT1-specific TCR (TCRC4 for clinical use.
The T cell subtype that is most involved in attacking abnormal cells is known as a CD8+ ‘killer’ T cell. Evaluation of safety and efficacy of transplant donor-derived CD8+ T cells carrying the HLA-A*0201-restricted WT1-specific TCRC4 in currently underway.
Dr. Aude Chapuis is an expert in hematopoietic stem cell transplantation and in developing novel ways to help a patient’s immune system target life-threatening viral infections and various malignancies. Building on positive results with adoptive transfer of T cells targeting specific antigens in HIV and melanoma.
At the Fred Hutchinson Cancer Research Center Dr. Chapuis laboratory is focused on understanding the factors associated with successful therapies so that adoptive T cells therapies can eliminate tumors with T cell receptors (TCRs) that bind specific target antigens, generating antigen-specific T cells and preparing certified T cell products for patients.
Clinical trials and correlative laboratory studies are underway for patients with myeloid leukemia and Merkel cell carcinoma.
The Fruits of Our Labor
ACQUIRED CANCER RESISTANCE TO COMBINATION IMMUNOTHERAPY FROM TRANSCRIPTIONAL LOSS OF CLASS I HLA
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor–immune interfaces through defined T cell/antigen interactions. Here we report single cell RNA sequencing identified dynamic transcriptional suppression of the specific HLA genes presenting the targeted viral epitope in the resistant tumor as a consequence of intense CD8-mediated immunologic pressure; this is distinguished from genetic HLA-loss by its reversibility with drugs.
Nature Communication 2018
TRACKING THE FATE AND ORIGIN OF CLINICALLY RELEVANT ADOPTIVELY TRANSFERRED CD8+ T CELLS IN VIVO
Science Immunology 2017
Adoptively transferred tumor-specific cells can mediate tumor regression in cancers refractory to conventional therapy. Autologous polyclonal tumor-specific cytotoxic T cells (CTL) generated from peripheral blood and infused into patients with metastatic melanoma show enhanced persistence, compared to equivalent numbers of more extensively expanded monoclonal CTL, and are associated with complete remissions (CR) in select patients. We applied high-throughput T cell receptor Vβ sequencing (HTTCS) to identify individual clonotypes within CTL products, track them in vivo post-infusion and then deduce the pre-adoptive transfer (endogenous) frequencies of cells ultimately responsible for tumor regression.