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 immunotherapy for patients with advanced cancer, including renal cell carcinoma. To determine the most appropriate method of activation for cancer immunotherapy in vitro antitumor activity of the 2 effector T-cell populations were compared.

Methods And Methods: The effector T-cell populations were generated concurrently by activation of peripheral blood mononuclear cells from patients with advanced renal cell carcinoma or other cancer using soluble anti-CD3 monoclonal antibody (3T cells) or anti-CD3 and anti-CD28 monoclonal antibodies immobilized on beads (3/28T cells). After 14-day culture the phenotype and 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 similar ability to kill various human tumor cell lines. Although both effector T-cell populations produced Th1-type cytokines upon re-stimulation, 3T cells secreted a higher level of interferon-gamma and tumor necrosis factor-alpha compared with 3/28T cells. Intracellular cytokine analysis demonstrated that the percent of cells producing interferon-gamma was higher in CD4(+), CD8(+), CD25(+), CD69(+) and CD45RO(+) 3T cells compared with 3/28T cells.

Conclusions: These data suggest that 3T cells may have increased efficacy as immunotherapy for patients with cancer due to higher levels of tumoricidal cytokine production than 3/28T cells.