The following summary is “A Novel B7-H6–Targeted IgG-Like T Cell–Engaging Antibody for the Treatment of Gastrointestinal Tumors” published in the December 2022 issue of Oncology by Zhang et al.
A significant unmet need exists for highly effective medicines to treat advanced-stage gastrointestinal malignancies. For this study, researchers looked at the anticancer efficacy of a new T cell-engaging antibody (B7-H6/CD3 ITE) that targets B7-H6, an antigen commonly expressed in gastrointestinal cancers. Through membrane proteomics and IHC analysis, investigators found that B7-H6 is overexpressed in gastrointestinal tumor tissues but not in normal tissues. In vitro co-culture tests, humanized mouse tumor models, and colorectal cancer precision cut tumor slice cultures were used to analyze the anticancer efficacy and mechanism of action of B7-H6/CD3 ITE.
Tissue samples from patients with colorectal cancer (98%) were found to express B7-H6, while those with gastric cancer (77%) and pancreatic cancer (63%). In addition, redirecting T cells towards B7-H6+ tumor cells via B7-H6/CD3 ITE led to B7-H6 dependent lysis of tumor cells, T cell activation, proliferation, and cytokine secretion in in vitro coculture assays, and T cell infiltration into tumor tissues, along with tumor regression, in in vivo colorectal cancer models.
Endogenous tumor-infiltrating immune cells secreted cytokines after being treated with B7-H6/CD3 ITE in cultures made from precision-cut tumor slices obtained from patients with colorectal cancer. The efficiency of B7-H6/CD3 ITE was further increased when combined with anti-PD-1. In addition, antitumor activity was observed in in vitro, in vivo, and human tumor slice cultures, providing evidence for further investigation in a clinical study of the B7-H6/CD3 ITE.