The immune cell we have cloned has a classical two-protein T-cell receptor (TCR), but does not use any of a set of standard proteins, the Major Histocompatability Locus (MHC) as nearly all other T-cells use. It can recognize 10 of 11 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. We have also begun an experimental protocol with this receptor 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.
| 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 |
