The unique activity of any individual T-cell is determined by antigen specific T-cell receptors (TCR) expressed on the cell surface. T-lymphocytes can be isolated from both human and murine tumors which are capable of specifically recognizing and lysing autologous tumor in vitro. These cytotoxic T-cells, known as tumor infiltrating Iymphocytes (TIL) can be expanded in vitro with IL-2, and have been used therapeutically in some patients with advanced disease. Recent evidence has indicated that melanoma specific TIL derived from HLA-A2+ patients not only recognize and lyse autologous tumor, but also can specifically lyse melanoma obtained from different HLA-A2+ patients. These T-cells are capable of recognizing tumor cells, and potentially a common tumor antigen, as a result of the tumor specific TCR present on their cell surface.
The major thrust of this research laboratory has been to isolate and identify tumor specific TCRs, and also to design vectors capable of transferring TCR cDNA (and therefore tumor recognition) to an alternate cell line. The ability to identify and isolate a tumor specific TCR provides some unique research opportunities including in vivo evaluation of factors inhibiting successful T-cell recognition of tumor antigen, in vitro tumor antigen screen/identification in new tumor histologies, and creation of adjuvant or therapeutic agents utilizing one or more tumor specific TCR(s) inserted into a patient's own autologous T-cells. This research utilizes molecular biology cloning techniques, current PCR technology, and immunology methods. Through the analysis of T-cell receptor/tumor interaction, we hope to better understand the factors which allow tumor growth in vivo as a basis for designing more potent anti-cancer treatments.
Cole DJ, Sanda MG, Yang JC, Schwarkenruber DS, Weber J, Ettinghausen SE, PockaJ BA, Kim Hl, Levin RD, Pogrebniak HW, Balkissoon J, Fenton RM, DeBarge, LR, Kaye J, Rosenberg SA, Parkinson DR: Phase I open trial of continuous intravenous rhM-CSF in patients with metastatic cancer. J Natl Cancer Inst, Vol 86(1): 39-45, 1994.
Cole DJ, Nishimura M, ShDyansky J, Yannelli J, Custer M, Rosenberg SA: Identification and transfer of funtional TCR alpha and beta chains frc1n tumor specific murine T-cell clones to alternative effector cells (current investigation).