Adoptive immunotherapy for advanced cancer patients using in vitro activated cytotoxic T lymphocytes

Background and Objectives: We evaluated the clinical efficacy of adoptive i mmunotherapy using in vitro activated cytotoxic T lymphocytes (CTL) in the treatment of patients with advanced cancer. Methods: CTL were induced with the mixed lymphocyte and tumor cell culture method, in which lymphocytes isolated from patient peripheral blood mononuc lear cells were mixed with inactivated autologous tumor cells. Activated ly mphocytes were administered intravenously to 11 patients once every 2 weeks for 10 weeks (i.e., 5 doses). Results: Tumor reduction and decreased tumor marker were observed in 4 pati ents. Notably, successful CTL induction was identified in all of these pati ents. In patients who did not show induction of CTL response, a decreased p roportion of lymphocytes, especially CD8+ cells, and increased levels of CD 14(+) cells were frequently observed. Fluorescence-activated cell sorter an alysis indicated that expression of HLA class I and costimulatory factor B7 -1 molecules was diminished on tumor cells. This was partly recovered with interferon-gamma, which resulted in successful induction of a CTL response. Conclusions: It was suggested that in vitro CTL induction is difficult in p atients with advanced cancer. However, once the cells were induced successf ully, some favorable clinical effects were seen by the adoptive transfer of such cell populations. (C) 1999 Wiley-Liss, Inc.