The tumor targeted superantigen ABR-217620 selectively engages TRBV7-9 and exploits TCR-pMHC affinity mimicry in mediating T cell cytotoxicity.

ABSTRACT: The T lymphocytes are the most important effector cells in immunotherapy of cancer. The conceptual objective for developing the tumor targeted superantigen (TTS) ABR-217620 (naptumomab estafenatox, 5T4Fab-SEA/E-120), now in phase 3 studies for advanced renal cell cancer, was to selectively coat tumor cells with cytotoxic T lymphocytes (CTL) target structures functionally similar to natural CTL pMHC target molecules. Here we present data showing that the molecular basis for the anti-tumor activity by ABR-217620 resides in the distinct interaction between the T cell receptor β variable (TRBV) 7-9 and the engineered superantigen (Sag) SEA/E-120 in the fusion protein bound to the 5T4 antigen on tumor cells. Multimeric but not monomeric ABR-217620 selectively stains TRBV7-9 expressing T lymphoc

SUBMITTER: Hedlund G 

PROVIDER: S-EPMC3806850 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature