Multiplexed-engineered, iPSC-derived CAR T Cell Targets Proteins Expressed on Cancer Cells in Response to Cellular Stress and Malignant Transformation
Off-the-shelf Product Candidate Incorporates Novel Sword & Shield Technology Designed to Promote Functional Persistence without Conditioning Chemotherapy
FT836 Preclinical Data Shows Robust Antigen-mediated Expansion, Functional Persistence, and Durable Anti-tumor Activity in the Presence of Alloreactive T Cells
SAN DIEGO, CA, USA I November 08, 2024 I Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, today presented initial preclinical data for FT836, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB) at the 2024 Society of Immunotherapy of Cancer (SITC) 39th Annual Meeting being held in Houston, TX on November 6-10, 2024. The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation, and is detectable across many types of cancer cells with limited expression on healthy tissue. FT836 incorporates multiple next-generation synthetic controls of CAR T-cell function including the Company’s novel Sword & Shield technology, which is comprised of a constellation of genetic edits that both target and evade host alloreactive immune cells and is designed to promote functional persistence of off-the-shelf CAR T-cell therapies without conditioning chemotherapy.
“The novel suite of synthetic controls incorporated into FT836 is intended to address critical challenges that have limited CAR T-cell safety and efficacy in treating solid tumors including on-target, off-tumor toxicity, effector cell suppression in the tumor microenvironment, tumor heterogeneity, and limited functional persistence,” said Bob Valamehr, Ph.D., President of Research & Development of Fate Therapeutics. “Our FT836 preclinical data presented today at SITC support the pan-cancer activity of MICA/B targeting, and indicate that our next-generation, iPSC-derived CAR T-cell platform has the potential to drive potent and durable anti-tumor activity without the need for administration of conditioning chemotherapy to deplete host immune cells.”
Preclinical Data
MICA/B targeting is emerging as a novel cancer-specific strategy to attack a wide range of solid tumors, however, proteolytic cleavage and shedding of MICA/B at the membrane-proximal α3 domain is a common mechanism of cancer resistance and escape from canonical NKG2D-mediated recognition. FT836 is designed to uniquely target and bind the α3 domain, which has been shown to stabilize MICA/B expression and induce robust cytolytic killing of tumor cells. At an oral presentation today at SITC entitled “Development of an Off-the-Shelf, MICA/B Targeting CAR T Cell to Overcome Pan-tumor Escape Mechanism for Solid Tumors”, scientists from the Company highlighted that FT836 exerted potent and durable anti-tumor activity in vivo across a broad array of solid tumors. In addition, treatment of tumor cells with chemotherapy or radiation therapy in vitro elicited an increase in MICA/B expression and further enhanced the cytolytic activity of FT836, indicating the potential for combination with standard-of-care regimens used for the treatment of solid tumors.
Novel Sword & Shield Technology
FT836 is also the Company’s first product candidate to incorporate its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO), to both target and evade host alloreactive immune cells. In preclinical studies presented at SITC, iPSC-derived Sword & Shield CAR T cells demonstrated functional persistence and durable anti-tumor activity in vivo that was uniquely maintained upon supraphysiological challenge with alloreactive T cells, indicating the potential of Sword & Shield CAR T cells to thrive without administration of conditioning chemotherapy to deplete host immune cells. The Company’s novel Sword & Shield technology was also featured in a poster presentation at SITC entitled “Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy”.
About Fate Therapeutics’ iPSC Product Platform
Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications.
About Fate Therapeutics, Inc.
Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company’s pipeline includes iPSC-derived natural killer (NK) cell and T-cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com.
SOURCE: Fate Therapeutics
Post Views: 1,458
Multiplexed-engineered, iPSC-derived CAR T Cell Targets Proteins Expressed on Cancer Cells in Response to Cellular Stress and Malignant Transformation
Off-the-shelf Product Candidate Incorporates Novel Sword & Shield Technology Designed to Promote Functional Persistence without Conditioning Chemotherapy
FT836 Preclinical Data Shows Robust Antigen-mediated Expansion, Functional Persistence, and Durable Anti-tumor Activity in the Presence of Alloreactive T Cells
SAN DIEGO, CA, USA I November 08, 2024 I Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, today presented initial preclinical data for FT836, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB) at the 2024 Society of Immunotherapy of Cancer (SITC) 39th Annual Meeting being held in Houston, TX on November 6-10, 2024. The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation, and is detectable across many types of cancer cells with limited expression on healthy tissue. FT836 incorporates multiple next-generation synthetic controls of CAR T-cell function including the Company’s novel Sword & Shield technology, which is comprised of a constellation of genetic edits that both target and evade host alloreactive immune cells and is designed to promote functional persistence of off-the-shelf CAR T-cell therapies without conditioning chemotherapy.
“The novel suite of synthetic controls incorporated into FT836 is intended to address critical challenges that have limited CAR T-cell safety and efficacy in treating solid tumors including on-target, off-tumor toxicity, effector cell suppression in the tumor microenvironment, tumor heterogeneity, and limited functional persistence,” said Bob Valamehr, Ph.D., President of Research & Development of Fate Therapeutics. “Our FT836 preclinical data presented today at SITC support the pan-cancer activity of MICA/B targeting, and indicate that our next-generation, iPSC-derived CAR T-cell platform has the potential to drive potent and durable anti-tumor activity without the need for administration of conditioning chemotherapy to deplete host immune cells.”
Preclinical Data
MICA/B targeting is emerging as a novel cancer-specific strategy to attack a wide range of solid tumors, however, proteolytic cleavage and shedding of MICA/B at the membrane-proximal α3 domain is a common mechanism of cancer resistance and escape from canonical NKG2D-mediated recognition. FT836 is designed to uniquely target and bind the α3 domain, which has been shown to stabilize MICA/B expression and induce robust cytolytic killing of tumor cells. At an oral presentation today at SITC entitled “Development of an Off-the-Shelf, MICA/B Targeting CAR T Cell to Overcome Pan-tumor Escape Mechanism for Solid Tumors”, scientists from the Company highlighted that FT836 exerted potent and durable anti-tumor activity in vivo across a broad array of solid tumors. In addition, treatment of tumor cells with chemotherapy or radiation therapy in vitro elicited an increase in MICA/B expression and further enhanced the cytolytic activity of FT836, indicating the potential for combination with standard-of-care regimens used for the treatment of solid tumors.
Novel Sword & Shield Technology
FT836 is also the Company’s first product candidate to incorporate its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO), to both target and evade host alloreactive immune cells. In preclinical studies presented at SITC, iPSC-derived Sword & Shield CAR T cells demonstrated functional persistence and durable anti-tumor activity in vivo that was uniquely maintained upon supraphysiological challenge with alloreactive T cells, indicating the potential of Sword & Shield CAR T cells to thrive without administration of conditioning chemotherapy to deplete host immune cells. The Company’s novel Sword & Shield technology was also featured in a poster presentation at SITC entitled “Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy”.
About Fate Therapeutics’ iPSC Product Platform
Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications.
About Fate Therapeutics, Inc.
Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company’s pipeline includes iPSC-derived natural killer (NK) cell and T-cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com.
SOURCE: Fate Therapeutics
Post Views: 1,458
