Peptide-scFv antigen recognition domains effectively confer CAR T cell multiantigen specificity.

ABSTRACT: The emergence of immune escape is a significant roadblock to developing effective chimeric antigen receptor (CAR) T cell therapies against hematological malignancies, including acute myeloid leukemia (AML). Here, we demonstrate feasibility of targeting two antigens simultaneously by combining a GRP78-specific peptide antigen recognition domain with a CD123-specific scFv to generate a peptide-scFv bispecific antigen recognition domain (78.123). To achieve this, we test linkers with varying length and flexibility and perform immunophenotypic and functional characterization. We demonstrate that bispecific CAR T cells successfully recognize and kill tumor cells that express GRP78, CD123, or both antigens and have improved antitumor activity compared to their monospecific counterparts when both

SUBMITTER: Zoine JT 

PROVIDER: S-EPMC10897625 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature