Adoptive transfer of cytotoxic T lymphocytes induced by CD86-transfected tumor cells suppresses multi-organ metastases of C1300 neuroblastoma in mice.
In this study, we examined the therapeutic antitumor effect of cytotoxic T lymphocytes (CTL) generated against CD86-transfected mouse neuroblastoma C1300. We first generated the transfectant, CD86 + C1300, expressing a high level of mouse CD86 on the cell surface. While CD86 + C1300 cells were rejected in syngeneic A/J mice when inoculated subcutaneously, neither vaccination nor any therapeutic antitumor effect was obtained, implying that C1300 may be a poorly immunogenic tumor. However, in vitro stimulation of splenocytes from either C1300-bearing or CD86 + C1300-rejecting mice with CD86 + C1300 cells resulted in remarkable CTL activity against C1300 cells. The CTL activity induced by CD86 + C1300 was 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, ovary, lymph node and bone marrow. To examine the therapeutic effect of CTL in this metastasis model, CTL induced by parental or CD86 + C1300 cells were administrated into C1300-bearing mice. Adoptive transfer of CD86 + C1300-induced CTL resulted in marked elimination of multi-organ metastases and prolonged survival in almost all mice, 70% of which survived indefinitely. These results indicate that adoptive transfer of CTL induced by CD86-transfected tumor cells in vitro would be effective and useful for tumor immunotherapy against poorly immunogenic tumors.
Enomoto
A
A
Department of Pediatrics, Juntendo University School of Medicine, Tokyo, Japan.
Kato
K
K
Yagita
H
H
Okumura
K
K
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D016219:Immunotherapy, Adoptive / Q000592:standards*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000556:secondary / Q000628:therapy*; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000556:secondary / Q000628:therapy*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051940:B7-2 Antigen; D017252:CD3 Complex; D016827:CD8 Antigens; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins