De "belegger" blijkt vandaag niet gecharmeerd van de nieuwste loot aan de stam van Fate: - 3,5%. Het is gelukkig geen EGFR geworden.
Fate Therapeutics announces FDA clearance for FT536
Fate Therapeutics announced that the U.S. Food and Drug Administration has cleared the Company's Investigational New Drug application for FT536, an off-the-shelf, multiplexed-engineered, iPSC-derived, chimeric antigen receptor NK cell product candidate. FT536 is derived from a clonal master induced pluripotent stem cell line engineered with four functional elements, including a novel CAR that uniquely targets the alpha3 domain of the major histocompatibility complex class I related proteins A and B. MICA and MICB are stress proteins that are expressed at high levels on many solid tumors. The Company plans to initiate clinical investigation of FT536 as a monotherapy and in combination with tumor-targeting monoclonal antibody therapy for the treatment of multiple solid tumor indications. FT536 also incorporates a novel high-affinity 158V, non-cleavable CD16 Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion that augments NK cell activity; and the deletion of the CD38 gene, which promotes persistence and function in high oxidative stress environments such as the suppressive tumor microenvironment. The multi-center Phase 1 clinical trial of FT536 is designed to determine the maximum tolerated dose of FT536 and assess its safety and clinical activity as monotherapy and in combination with one of an array of five monoclonal antibodies for the treatment of advanced solid tumors. Eligible tumor types include advanced non-small cell lung cancer, colorectal cancer, head and neck cancer, gastric cancer, breast cancer, ovarian cancer, and pancreatic cancer. The Phase 1 clinical protocol allows for administration of FT536 initially in up to two, 30-day cycles, with each cycle consisting of three days of conditioning chemotherapy and three weekly doses of FT536. Patients with clinical benefit may be re-treated with up to two additional cycles. Furthermore, for those patients that achieve initial clinical response, additional treatment with FT536 may be administered following disease progression. The off-the-shelf treatment regimen is designed to be administered in the outpatient setting. The expression of MICA and MICB proteins, which is induced by cellular stress, damage or transformation, has been reported for many solid tumor types. Cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can recognize and bind the membrane-distal alpha1 and alpha2 domains of MICA/B, activating a potent cytotoxic response. However, cancer cells frequently evade immune cell recognition by proteolytic shedding of the alpha1 and alpha2 domains of MICA/B. A recent publication in Science (DOI:10.1126/science.aao0505) by 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 antibody targeting of the MICA/B alpha3 domains specifically prevents MICA/B shedding and restores NK cell-mediated immunity. Additionally, in a more recent publication in Cancer Immunology Research, Dr. Wucherpfennig also demonstrated that cancers with B2M and JAK1 inactivating mutations resulting in loss of MHC Class I expression can be effectively targeted with MICA/B alpha3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors resistant to cytotoxic T cells. The Company's 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.