Characterizing a novel tumor recognition mechanism

Division Of Basic Sciences - Nci

Investigators

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Abstract

The immune cell we have cloned has a classical two-protein T-cell receptor (TCR), but is able to recognize nearly all human renal cancers tested, despite their not sharing any of the (MHC) molecules normally needed for immune recognition. We have recently shown and published that this T-cell receptor recognizes the TRAIL molecule bound to one of its usual receptors, DR4. We also indentifed other molecules that particpate in tumor recognition. In parallel with this scientific investigation, we optimized the native TCR and have been able to use genetic engineering to introduce these improved TCRs into the immune cells of any RCC patient and show they can now recognize and react with most renal cancers. If toxicity can be reduced, we would like to continue giving genetically constructed cells to patients who have exhausted standard therapies for metastatic renal cancer to see if we can see regression of their tumors.