Synapse

Antigen

Cytotoxic T cell

Neuroscience

Receptor

Jurkat cells

Lytic cycle

Chemistry

T-cell receptor

In vitro

Immunology

Virus

T cell

Chimeric antigen receptor

Cancer research

Biochemistry

Biology

Immune system

Cell biology

Immunological synapse

Proceedings of the National Academy of Sciences

Significance Davenport et al. discovered that the chimeric antigen receptor (CAR) immune synapse structure is different from the T cell receptor (TCR) synapse. The CAR immune synapse formed a disorganized pattern of Lck and more rapidly recruited lytic granules compared with the TCR. The differing immune synapse correlated with faster killing of tumor target cells and detachment from dying tumor cells by CAR-T cells. These findings provide a mechanism whereby CAR-T cells can effectively reduce large tumor burden in patients. This study will form a basis upon which to compare future receptor design to modulate signaling and programming of cytotoxic CAR-T cells to improve treatment of solid cancers.

Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity