O8.2 - Putting adoptive T cell therapy on the path to regulatory approval

Abstract

ABSTRACT There is compelling evidence that the adoptive cell transfer (ACT) of large numbers of tumor-specific T cells induces durable tumor regressions in patients with different cancers. Experiences in melanoma adoptively transferring tumor-infiltrating lymphocytes (TIL) and T cell receptor (TCR) engineered T cells, and in B cell leukemias and lymphomas adoptively transferring CD19 chimeric antigen receptor (CD19) engineered T cells, have attracted great interest to this field of personalized cell therapy. As there is no question whether the approach is therapeutic, then the main issue is how it can be developed to become a broadly applied therapy. There are two potential avenues to develop ACT clinically for broad applicability: i) the blood bank model, where the manufacture of T cells directed to cancer is provided as a service as it is for blood transfusions or hematopoietic stem cells, and ii) private companies manufacturing patient-specific T cell preparations off-site for reinfusion into patients. Some hospitals and academic groups have established their own CD19 CAR ACT programs, with many more planning to provide this therapy to their patients. In addition, several companies are developing programs of ACT. As a cellular therapy platform, the use of CAR and TCR engineering seems more amenable to commercialization than TIL therapy. TILs are obtained from tumor biopsies and T cells are expanded from them. The input tissue for TIL therapy can be a tiny core biopsy or a large surgical resection, and it may include multiple different contaminants. Not all tumors contain TILs and not all TILs expand ex vivo. As opposed to TIL therapy, CAR or TCR engineering starts from the uniform collection of peripheral blood T lymphocytes by a standard leukapheresis, and these cells are expanded and genetically engineered ex vivo in a reproducible manner. In conclusion, therapies for cancer that work should be approved by regulatory bodies, and there is little doubt that ACT will eventually become an approved mode of therapy. Generating the data from multicenter studies for full regulatory approval requires the involvement of biopharmaceutical industry, but an established business model for a personalized cell therapy does not currently exist.