The immune cell we have cloned has a classical two-chain T-cell receptor (TCR), but is not restricted by MHC. It can recognize 10 of 11 human renal cancers tested, despite their not sharing a common HLA locus. This T-cells does not react with matched EBV-B cells, normal fibroblasts or other T-cells. Its lack of MHC restriction, circumvents the severe restriction on the utility of classical T-cell recognition that requires that susceptible tumors express a specific HLA molecule for recognition. Our studies have shown that introduction of the genes which encode this TCR into any third-party peripheral blood lymphocyte confers tumor recognition, showing that tumor recognition is clearly TCR mediated. Furthermore, the recognition of tumors is markedly enhanced by exposure to the target cell to TNF-related apoptosis inducing ligand (TRAIL), a molecule with significant tumor specificity, also being explored as a novel reagent in cancer trials. Current efforts are attempting to define what other molecules besides TRAIL participate in this recognition and define the target antigen. Concurrently, we are developing vectors and enhanced versions of the TCR for possible use in future clinical gene therapy trials.
