Fate Therapeutics Announces Preclinical Data Presentation of Novel CAR MICA/B Cell-based Cancer Immunotherapy Program at the 2020 ASGCT Annual Meeting
Program Incorporates New CAR Constructs Designed to Specifically Target the Pan-tumor Associated Stress Proteins MICA and MICB
Proprietary Binding Domains Shown to Overcome MICA/B Shedding, a Common Mechanism of Tumor Cell Escape Broadly Observed Across Solid Tumors
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“MICA and MICB are emerging as exciting pan-cancer immunotherapy targets, and we are pleased that our engineered iPSC-derived CAR-MICA/B NK cells have shown potent anti-tumor activity in preclinical studies,” said
While it is well known that tumor resistance to cytotoxic T cells is mediated by loss of MHC Class I expression, proteolytic shedding of the α1 and α2 domains of MICA/B expressed on tumor cells is a common mechanism of NK cell evasion. A recent publication in Science (DOI:10.1126/science.aao0505) by
Using a clonal master induced pluripotent stem cell (iPSC) line previously engineered with an expression cassette introduced into the CD38 locus that encodes for a high-affinity, non-cleavable CD16 Fc receptor and an IL-15 receptor fusion, scientists from
Other Company abstracts selected for presentation at ASGCT include the derivation of clonal master engineered iPSC lines for the Company’s FT576 product candidate, an off-the-shelf, multi-antigen targeted CAR-BCMA NK cell engineered with four anti-tumor modalities for the treatment of multiple myeloma; and a study of various expression systems for the generation, engineering and cryopreservation of clonal master engineered iPSC lines.
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, advanced 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. 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 cycles of 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 300 issued patents and 150 pending patent applications.
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of and plans related to the Company’s NK and T-cell product candidates and preclinical research and development programs, and the scope and enforceability of the Company’s intellectual property portfolio. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that results observed in preclinical studies of its product candidates may not be replicated in ongoing or future clinical trials or studies, the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects, and the risk that any of the patents owed or licensed by the Company may be challenged and that such a challenge may be successful, resulting in loss of any such patent or loss or reduction in the scope of one or more of the claims of a challenged patent. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the
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Source: Fate Therapeutics, Inc.