Engineering T Cells for Safe and Effective Cancer Immunotherapy

Sunday, February 14, 2016: 8:00 AM-9:30 AM
Harding (Marriott Wardman Park)
Stanley Riddell, Fred Hutchinson Cancer Research Center, Seattle, WA
Engineering T cells for safe and effective cancer immunotherapy

Stanley Riddell, Fred Hutchinson Cancer Research Center

 Recent advances in understanding the mechanisms by which cancers evade immune recognition have led to new immunotherapies that have the potential to transform the management of many human cancers. T lymphocytes are critical to adaptive immunity to pathogens and tumors because of their longevity and ability to clonally expand, and are increasingly being manipulated for the treatment of human diseases, including cancer. Advances in gene transfer methods using viral and non-viral delivery have made it possible to introduce genes into T cells that encode natural T cell or synthetic receptors that bind to molecules on the surface of cancer cells, and redirect the specificity of the T cell to mediate tumor cell destruction. Several groups, including our own have shown that the adoptive transfer of T cells that are genetically engineered to express a synthetic chimeric antigen receptor (CAR) that targets the B cell lineage molecule CD19 exert potent antitumor activity in patients with chemotherapy refractory B-cell malignances including acute lymphoblastic leukemia, chronic lymphocytic leukemia and non-Hodgkin’s lymphoma. T cells exist in different subsets with cell intrinsic properties that affect their ability to persist and proliferate after adoptive transfer. By selecting T cells with optimal attributes for genetic modification and adoptive therapy, eradication of massive tumor burdens can be accomplished with remarkably low doses of engineered T cells, and with predictable T cell expansion kinetics and toxicity. A remaining challenge is to identify target molecules that are expressed on common human cancers and to design receptors that safely target them so that adoptive immunotherapy with genetically redirected T cells can be broadly applied.