On October 1, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported that one oral and four poster presentations for the Company’s induced pluripotent stem cell (iPSC) product platform were accepted for presentation at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 10-14, 2021 (Press release, Fate Therapeutics, OCT 1, 2021, View Source [SID1234590638]).
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The oral presentation will highlight preclinical data for FT536, the Company’s off-the-shelf, multiplexed-engineered, iPSC-derived, chimeric antigen receptor (CAR) NK cell product candidate that uniquely targets the α3 domain of the MHC class I related proteins A (MICA) and B (MICB). In a recent publication in Cancer Immunology Research (DOI: 10.1158/2326-6066.CIR-19-0483), Kai W. Wucherpfennig, M.D., Ph.D., Chair of the Department of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and co-leader of the Cancer Immunology Program at Dana-Farber / Harvard Cancer Center, demonstrated that cancers with loss of MHC Class I expression can be effectively targeted with MICA/B α3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors. The FT536 program is supported by an exclusive license from the Dana-Farber Cancer Institute to intellectual property covering novel antibody fragments binding MICA/B for iPSC-derived cellular therapeutics. The Company expects to submit an Investigational New Drug (IND) application for FT536 in the fourth quarter of 2021 for the treatment of advanced solid tumors, including in combination with monoclonal antibody therapy.
Poster presentations at SITC (Free SITC Whitepaper) will include preclinical data on new functional elements that the Company is evaluating for incorporation into its iPSC-derived cell product candidates for solid tumors. These synthetic features include engineered chemokine receptors, which the Company has demonstrated can enhance the trafficking and homing of iPSC-derived CAR T cells to tumors, and synthetic TGFβ re-direct receptors, which the Company has shown can exploit immuno-suppressive cytokines found in the tumor microenvironment to potentiate iPSC-derived CAR T cells and improve anti-tumor activity.
Oral Presentation
FT536 Path to IND: Ubiquitous targeting of solid tumors with an off-the-shelf, first-of-kind MICA/B-specific CAR-iNK cellular immunotherapy
Abstract #: 117
Session 212: Cellular Therapies; November 13, 3:40 pm – 4:55 pm EST
Poster Presentation
Synthetic re-direction of TGFβ receptors as a novel strategy to enhance the anti-tumor activity of iPSC-derived CAR-T cells in solid tumors
Abstract #: 138
Chemokine receptor engineering enhances trafficking and homing of primary and iPSC-derived CAR-T cells to solid tumors
Abstract #: 120
Off-the-shelf, engineered iPSC-derived NK cells mediate potent cytotoxic activity against primary glioblastoma cells and promote durable long-term survival in vivo
Abstract #: 169
Novel FcyR recombinant fusion facilitates antibody arming of engineered iPSC-derived NK cells to enhance targeting and killing of ovarian cancer cells
Abstract #: 197
About MICA and MICB Proteins
The major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB) are induced by cellular stress, damage or transformation, and the expression of MICA and MICB proteins has been reported for many tumor types. Cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can detect and bind the membrane-distal α1 and α2 domains of MICA/B, activating a potent cytotoxic response. However, cancer cells frequently evade immune cell recognition by proteolytic shedding of the α1 and α2 domains of MICA/B. The clinical importance of proteolytic shedding is reflected in the association of high serum concentrations of shed MICA/B with disease progression in many solid tumors. Several recent publications have shown that therapeutic antibodies targeting the membrane-proximal α3 domain strongly inhibited MICA/B shedding, resulting in a substantial increase in the cell surface density of MICA/B and restoration of NK cell-mediated tumor immunity (DOI:10.1126/science.aao0505). Therapeutic approaches aimed at targeting the α3 domain of MICA/B therefore represent a potentially promising novel strategy to overcome this prominent evasion mechanism as a means of restoring anti-tumor immunity.
About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.