Antibody-based redirection of universal Fabrack-CAR T cells selectively kill antigen bearing tumor cells.

ABSTRACT:

Background

Chimeric antigen receptor (CAR) T cells engineered to recognize and target tumor associated antigens have made a profound impact on the quality of life for many patients with cancer. However, tumor heterogeneity and intratumoral immune suppression reduce the efficacy of this approach, allowing for tumor cells devoid of the target antigen to seed disease recurrence. Here, we address the complexity of tumor heterogeneity by developing a universal CAR.

Method

We constructed a universal Fabrack-CAR with an extracellular domain composed of the non-tumor targeted, cyclic, twelve residue meditope peptide that binds specifically to an engineered binding pocket within the Fab arm of monoclonal antibodies (mAbs). As this site is readily grafted onto therapeutic mAbs, the an

SUBMITTER: Kuo YC 

PROVIDER: S-EPMC9214433 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature