Clinical benefit observed with immuno-oncology trials often depends on the unleashing of a pre-existing intrinsic T cell immune response in each cancer patient. The targets of these intrinsic T cells are commonly ascribed to recognition of patient-specific neoantigens that arose from cancer mutations.
PACT Pharma has developed the ability to selectively capture neoantigen-specific CD8+ T cells from peripheral blood of the patient. Leveraging this technology, PACT Pharma is developing personalized, autologous neo-epitope specific TCR-engineered T cell therapies for the eradication of solid tumors.
Briefly, using PACT's proprietary TCR isolation technology neoepitope-specific TCRs are cloned and autologous CD8+ and CD4+ T cells from the same patient with cancer are precision genome engineered (using a DNA-mediated (non-viral) method) to express the neoTCR. NeoTCR expressing T cells are then expanded in a manner that preserves a “younger” T cell phenotypes, resulting in a NeoTCR-P1 product in which the majority of the T cells exhibit T memory stem cell and T central memory phenotypes.
Upon cognate antigen encounter, NeoTCR-P1 rapidly differentiate into potent effector T cells. Engineered NeoTCR-P1 cells rapidly expand, secrete effector molecules such as perforin and granzyme B, and cytokines such as interferon-gamma (IFN-γ), IL-2 and TNF-alpha (TNF-α). Single cell secretome analysis demonstrates that NeoTCR-P1 cells are highly polyfunctional (secretion of two or more cytokines or effector proteins). These results demonstrate that PACT’s autologous ex vivo engineered NeoTCR-P1 T cells represent a highly personalized adoptive T cell therapy with potential to provide significant clinical benefit to subjects with solid tumors.
Citation Format: Barbara Sennino, Andrew Conroy, Bhamini Purandare, Adam Litterman, Kyle Jacoby, Robert Moot, William Lu, Diana Nguyen, Fabrizia Urbinati, Susan Foy, Theresa Hunter, Olivier Dalmas, Michael Bethune, Tim Park, Songming Peng, Alex Franzusoff, Stefanie Mandl. NeoTCR-P1, a novel neoepitope-specific adoptive cell therapy, consists of T cells with ‘younger’ phenotypes that rapidly proliferate and kill target cells upon recognition of cognate antigen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1433.