HLA-A∗02-gated safety switch for cancer therapy has exquisite specificity for its allelic target antigen.

ABSTRACT: Innovative cell-based therapies are important new weapons in the fight against difficult-to-treat cancers. One promising strategy involves cell therapies equipped with multiple receptors to integrate signals from more than one antigen. We developed a specific embodiment of this approach called Tmod, a two-receptor system that combines activating and inhibitory inputs to distinguish between tumor and normal cells. The selectivity of Tmod is enforced by the inhibitory receptor (blocker) that recognizes an antigen, such as an HLA allele, whose expression is absent from tumors because of loss of heterozygosity. Although unwanted cross-reactivity of the blocker likely reduces efficacy rather than safety, it is important to verify the blocker's specificity. We have tested an A∗02-directed blocke

SUBMITTER: Mock JY 

PROVIDER: S-EPMC9619369 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature