T cells activated in vitro as immunotherapy for renal, cell carcinoma: Characterization of 2 effector T-cell populations

Purpose: Effector T cell populations generated using 2 methods of in vitro activation are currently being tested in separate clinical trials as immuno therapy for patients with advanced cancer, including renal cell carcinoma. To determine the most appropriate method of activation for cancer immunothe rapy in vitro antitumor activity of the 2 effector T-cell populations were compared. Materials and Methods: The effector T-cell populations were generated concu rrently by activation of peripheral blood mononuclear cells from patients w ith advanced renal cell carcinoma or other cancer using soluble anti-CDS mo noclonal antibody (3T cells) or anti-CD3 and anti-CD28 monoclonal antibodie s immobilized on beads (3/28T cells). After 14-day culture the phenotype an d functional activity of the cells were tested. Results: Fold expansion of CD4(+) cells for 3T cultures was lower than for 3/28T cultures but expansion of CD8(+) cells was similar for both cultures. Expression of CD69 was higher on 3T cells. 3T and 3/28T cells exhibited si milar ability to kill various human tumor cell lines. Although both effecto r T-cell populations produced Th1-type cytokines upon re-stimulation, 3T ce lls secreted a higher level of interferon-gamma and tumor necrosis factor-a compared with 3/28T cells. Intracellular cytokine analysis demonstrated th at the percent of cells producing interferon-gamma was higher in CD4(+), CD 8(+), CD25(+), CD69(+) and CD45RO(+) 3T cells compared with 3/28T cells. Conclusions: These data suggest that 3T cells may have increased efficacy a s immunotherapy for patients with cancer due to higher levels of tumoricida l cytokine production than 3/28T cells.