ADAPTIVE TRANSFER OF CYTOTOXIC T-LYMPHOCYTES INDUCED BY CD86-TRANSFECTED TUMOR-CELLS SUPPRESSES MULTIORGAN METASTASES OF C1300 NEUROBLASTOMA IN MICE

In this study, we examined the therapeutic antitumor effect of cytotox ic T lymphocytes (CTL) generated against CD86-transfected mouse neurob lastoma C1300. We first generated the transfectant, CD86+C1300, expres sing a high level of mouse CD86 on the cell surface. While CD86+C1300 cells were rejected in syngeneic A/J mice when inoculated subcutaneous ly, neither vaccination nor any therapeutic antitumor effect was obtai ned, implying that C1300 may be a poorly immunogenic tumor. However, i n vitro stimulation of splenocytes from either C1300-bearing or CD86+C 1300-rejecting mice with CD86+C1300 cells resulted in remarkable CTL a ctivity against C1300 cells. The CTL activity induced by CD86+C1300 wa s mediated by T cell receptor/CD3 and CD8 and was further enhanced by the addition of interleukin-2. Intravenous inoculation of C1300 cells led to multiple organ metastases including the liver, lung, kidney, ov ary, lymph node and bone marrow. To examine the therapeutic effect of CTL in this metastasis model, CTL induced by parental or CD86+C1300 ce lls were administrated into C1300-bearing mice. Adoptive transfer of C D86+C1300-induced CTL resulted in marked elimination of multi-organ me tastases and prolonged survival in almost all mice, 70% of which survi ved indefinitely. These results indicate that adoptive transfer of CTL induced by CD86-transfected tumor cells in vitro would be effective a nd useful for tumor immunotherapy against poorly immunogenic tumors.