Induction of effective antitumor immunity in a mouse brain tumor model using B7-1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12.
Although tumor-specific T lymphocytes recognize tumor-associated antigens (TAA) present on their cell surface via major histocompatibility complex (MHC) molecules, T cells require other activating signals. These are provided by costimulatory molecules, including B7-1 (CD80), B7-2 (CD86) and intercellular adhesive molecule 1 (ICAM-1; CD54). Transfecting mouse tumor cell lines with the B7 gene can lead to primary tumor rejection and the establishment of protective immunity. However, some studies have shown that the B7 effect upon T-cell-dependent tumor immunity is limited. Therefore, we examined the antitumor effects of recombinant interleukin 12 (IL-12) and genetically engineered glioma cells expressing B7-1 or both B7-1 and ICAM-1. Vaccination of mice with B7-1-expressing tumor cells substantially inhibited the growth of subcutaneously inoculated gliomas but not those located in the brain. Vaccination with B7-1-expressing tumor cells and systemic recombinant IL-12 (rIL-12) was more effective than either B7-1-expressing tumor cells or rIL-12 alone. Our murine brain tumor model also showed that vaccination with tumor cells expressing both B7-1 and ICAM-1 combined with rIL-12 prolonged survival. We have demonstrated the therapeutic potential of vaccination with rIL-12 and tumor cells expressing both B7-1 and ICAM-1 in the control of glioma growth.
Joki
T
T
Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan.
Kikuchi
T
T
Akasaki
Y
Y
Saitoh
S
S
Abe
T
T
Ohno
T
T
D000818:Animals; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000235:genetics / Q000473:pathology; D006801:Humans; D016233:Immunotherapy, Active; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D018122:B7-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12