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. We have had partial success with adding receptors to T-cells that inhibit when they encounter a target that is on a normal tissue such as normal liver, but not on the tumor. This was not sufficient to assure safety, so we are also developing weaker receptors that will need some "help" and this would come from a second target that is on the tumor but not on most normal tissues. This work is still in progress.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Wang, Qiong J; Hanada, Ken-ichi; Feldman, Steven A et al. (2011) Development of a genetically-modified novel T-cell receptor for adoptive cell transfer against renal cell carcinoma. J Immunol Methods 366:43-51
Hanada, Ken-ichi; Wang, Qiong J; Inozume, Takashi et al. (2011) Molecular identification of an MHC-independent ligand recognized by a human {alpha}/{beta} T-cell receptor. Blood 117:4816-25