Fate Therapeutics Unveils Preclinical Data for FT836 CAR T-cell at 2024 SITC Meeting

In November 2024, at the 39th Annual Meeting of the Society of Immunotherapy of Cancer (SITC) in Houston, TX, Fate Therapeutics, Inc. shared initial preclinical data for their product candidate FT836. This innovative product is a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell targeting the major histocompatibility complex (MHC) proteins A (MICA) and B (MICB). These proteins are expressed on numerous cancer cells in response to cellular stress or malignant transformation, making them an effective target with minimal presence on healthy tissue.

FT836 utilizes several advanced synthetic controls for CAR T-cell function, including a new technology known as Sword & Shield. This technology comprises a set of genetic edits enabling the product to both target and evade host immune cells, designed to ensure the persistence of CAR T-cell therapies without the need for conditioning chemotherapy. This approach aims to address significant challenges in CAR T-cell therapy for solid tumors, including toxicity, suppression in the tumor environment, tumor variability, and limited persistence.

Bob Valamehr, Ph.D., President of Research & Development at Fate Therapeutics, emphasized that the novel controls integrated into FT836 seek to overcome these obstacles. The preclinical data supports MICA/B targeting's potential to drive robust and lasting anti-tumor activity without relying on conditioning chemotherapy.

MICA/B targeting is gaining recognition as a promising cancer-specific strategy to combat solid tumors. However, cancer cells often resist this strategy through proteolytic cleavage and shedding of MICA/B at the membrane-proximal α3 domain. FT836 aims to counter this by targeting and binding the α3 domain, stabilizing MICA/B expression and inducing strong cytolytic killing of tumor cells. During SITC, it was highlighted that FT836 demonstrated significant and durable anti-tumor activity across various solid tumors. Furthermore, treatments like chemotherapy or radiation therapy increased MICA/B expression and further boosted FT836's cytolytic activity, suggesting potential combination with standard cancer treatments.

FT836 is the first product candidate to incorporate Sword & Shield technology, which includes a 4-1BB-targeted CAR (ADR) and complete knock-out of CD58 (CD58KO). This combination is designed to both target and evade host immune cells, demonstrated to maintain functional persistence and anti-tumor activity even under physiological stress with alloreactive T cells. This indicates that Sword & Shield CAR T cells can thrive without the need for conditioning chemotherapy. This technology was also featured in a poster presentation at SITC, highlighting its comprehensive approach to promote the functional persistence of allogeneic cell therapies without conditioning chemotherapy.

Fate Therapeutics' platform uses human induced pluripotent stem cells (iPSCs) which have the unique ability to self-renew indefinitely and differentiate into any cell type. Their proprietary iPSC product platform combines multiplexed-engineering with single-cell selection to create clonal master iPSC lines. Similar to master cell lines used in biopharmaceutical production, these iPSC lines serve as a uniform cell source for manufacturing engineered cell products. These products are well-defined, can be stored for off-the-shelf availability, and can be combined with other therapies, potentially reaching a broad range of patients. This platform addresses many limitations of cell therapies derived from patient or donor cells and is backed by over 500 issued patents and 500 pending patent applications.

Fate Therapeutics is a clinical-stage biopharmaceutical company focused on developing induced pluripotent stem cell-derived cellular immunotherapies for cancer and autoimmune diseases. Their pipeline includes iPSC-derived natural killer (NK) and T-cell product candidates, designed with novel synthetic controls to provide multiple therapeutic mechanisms. The company is headquartered in San Diego, CA.