Fate Therapeutics, a clinical-stage biopharmaceutical company, has presented promising preclinical data for its novel CAR T-cell product candidate, FT836, at the 2024 Society of Immunotherapy of Cancer (SITC) Annual Meeting. FT836 targets major histocompatibility complex (MHC) proteins A (MICA) and B (MICB), offering a pan-tumor targeting approach with the potential to transform the treatment of solid tumors.
FT836's unique design targets the α3 domain of MICA/B, which stabilizes their expression and enhances cytolytic activity against tumor cells. This strategy overcomes the common mechanism of cancer resistance and escape from canonical NKG2D-mediated recognition. Preclinical data demonstrated potent and durable anti-tumor activity in vivo across a broad array of solid tumors, with chemotherapy or radiation therapy further enhancing FT836's cytolytic activity.
The novel Sword & Shield technology, incorporated into FT836, promotes functional persistence without conditioning chemotherapy. This technology combines a 4-1BB-targeted CAR (ADR) with the complete knock-out of CD58 (CD58KO), enabling FT836 CAR T cells to target and evade host alloreactive immune cells. Preclinical studies showed that iPSC-derived Sword & Shield CAR T cells maintained functional persistence and durable anti-tumor activity in vivo, even upon supraphysiological challenge with alloreactive T cells.
FT836's pan-tumor targeting strategy, enhanced cytolytic activity, and functional persistence without conditioning chemotherapy make it an attractive candidate for further clinical investigation. Fate Therapeutics' iPSC product platform, which combines multiplexed-engineering of human iPSCs with single-cell selection, enables the creation of clonal master iPSC lines for mass production of CAR T-cell therapies.
As Fate Therapeutics continues to advance FT836 and its other product candidates, investors should monitor the company's progress and consider its potential in the rapidly evolving field of cellular immunotherapies. The company's innovative approach to CAR T-cell therapy, along with its strategic partnerships and strong financial position, positions it well to capitalize on the growing demand for effective and safe cancer treatments.