A CRISPR Screen Reveals Resistance Mechanisms to CD3-Bispecific Antibody Therapy.

ABSTRACT: CD3-bispecific antibodies represent an important therapeutic strategy in oncology. These molecules work by redirecting cytotoxic T cells to antigen-bearing tumor cells. Although CD3-bispecific antibodies have been developed for several clinical indications, cases of cancer-derived resistance are an emerging limitation to the more generalized application of these molecules. Here, we devised whole-genome CRISPR screens to identify cancer resistance mechanisms to CD3-bispecific antibodies across multiple targets and cancer types. By validating the screen hits, we found that deficiency in IFNγ signaling has a prominent role in cancer resistance. IFNγ functioned by stimulating the expression of T-cell killing-related molecules in a cell type-specific manner. By assessing resistance to the clini

SUBMITTER: Liu SQ 

PROVIDER: S-EPMC8601150 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature