Integrating binding affinity and tonic signaling enables a rational CAR design for augmented T cell function.

ABSTRACT:

Background

The success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies has not yet translated into long-term elimination of solid tumors indicating the need for adequately tuning CAR T cell functionality.

Methods

We leveraged a translational pipeline including biophysical characterization and structural prediction of the CAR binding moiety, evaluation of cellular avidity, synapse formation, T cell motility, and functional capacities under repetitive target challenge and in sustained tumor control.

Results

As an example of clinical relevance, we derived a panel of anti-Her2 CARs covering a 4-log affinity range, all expected to target the same Her2 epitope. The same scFv mutations increased both antigen-specific affinity, cellular avidit

SUBMITTER: Barden M 

PROVIDER: S-EPMC11624832 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature