GT Biopharma, Fate present preclinical data on dual antigen targeting approach

GT Biopharma, Inc. (GTBP) announced the presentation of new preclinical data at the American Society of Hematology’s 64th Annual Meeting. The presentation highlights the potential of a novel dual antigen targeting approach for the treatment of acute myeloid leukemia by combining GT Biopharma’s Tri-specific Killer Engager with the induced pluripotent stem cell product platform of Fate Therapeutics, Inc. (FATE). The poster presentation titled, "A Novel Dual-Antigen Targeting Approach Enables Off-the-Shelf CAR NK Cells to Effectively Recognize and Eliminate the Heterogeneous Population Associated with AML," showcases the phenotypic and functional properties of multiplexed-engineered, iPSC-derived NK cells incorporating four functional modalities: a chimeric antigen receptor targeting the alpha3 domain of MICA/B; a high-affinity, non-cleavable CD16 Fc receptor; an IL-15 fusion receptor; and a knock-out of CD38. In preclinical models, alpha3 MICA/B iNK cells demonstrated potent anti-leukemic activity against AML cell lines, and the kinetics of cytotoxicity were enhanced in combination with an anti-CD33 TriKE. Conclusions: alpha3 MICA/B iNK cells exhibited antigen-specific activation in vitro as measured by interferon-gamma production and CD107a degranulation across a broad range of solid tumor cell lines. alpha3 MICA/B iNK cells demonstrated robust cytotoxicity in vitro against an array of AML cell lines, including those with proteolytic cleavage of the alpha1 and alpha2 domains of MICA/B, which is a known mechanism of tumor escape from NK cell cytotoxicity. The kinetics of cytotoxicity were enhanced in combination with GTB-3650, a second-generation anti-CD33 TriKE. An analysis of bone marrow aspirates from patients with AML showed high expression of the alpha3 domain, and low expression of the alpha1 and alpha2 domains, of MICA/B, suggesting that the combination of alpha3 MICA/B iNK cells with GTB-3650 may represent a unique dual-antigen targeting approach to improve anti-leukemic activity in patients with AML.