Data from A Novel B7-H6–Targeted IgG-Like T Cell–Engaging Antibody for the Treatment of Gastrointestinal Tumors

• DOI: 10.1158/1078-0432.c.6532800.v1
• Publication Date: 2023-04-01T05:59:47Z
• Authors: Wei Zhang; Aurélie Auguste; Xiaoyun Liao; Christian Walters...; Kathrin Bauer; Yu-Hsi Lin; Ling Yang; Farzaneh Sayedian; Markus Fabits; Michael Bergmann; Carina Binder; Leticia Corrales; Anne B. Vogt; Lindsey J. Hudson; Martin P. Barnes; Arnima Bisht; Craig Giragossian; Vladimir Voynov; Paul J. Adam; Susanne Hipp
• Keywords: Gastrointestinal cancer; Tumor Antigen; Tumor-infiltrating lymphocytes; Tumor M2-PK

<div>AbstractPurpose:<p>Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of novel T cell–engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, tumor-associated antigen that is expressed in tumors.</p>Experimental Design:<p>Membrane proteomics and IHC analysis identified B7-H6 as tumor tissues with no to very little expression normal tissues. The mode action B7-H6/CD3 ITE was evaluated <i>in vitro</i> coculture assays, humanized mouse models, colorectal cancer precision cut slice cultures.</p>Results:<p>B7-H6 detected 98% cancer, 77% gastric 63% pancreatic tissue samples. ITE-mediated redirection cells toward B7-H6–positive resulted B7-H6–dependent lysis cells, activation proliferation cytokine secretion infiltration into associated regression vivo</i> models. In primary patient-derived precision-cut cultures, treatment elicited by endogenous tumor-infiltrating immune cells. Combination anti-PD-1 further enhanced ITE.</p>Conclusion:<p>These data highlight potential induce cell–redirected recruitment noninflamed tissues, leading vitro, vivo</i>, human which supports evaluation clinical study.</p></div>