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

• Published in: International journal of cancer Vol. 82; no. 5; pp. 714 - 720
• Main Authors: Joki, Tatsuhiro, Kikuchi, Tetsuro, Akasaki, Yasuharu, Saitoh, Saburo, Abe, Toshiaki, Ohno, Tsuneya
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 27.08.1999; Wiley-Liss
• Subjects: AIDS/HIV; Animals; Antibodies, Neoplasm - therapeutic use; Antineoplastic agents; B7-1 Antigen - genetics; B7-1 Antigen - immunology; Biological and medical sciences; Brain Neoplasms - immunology; Brain Neoplasms - mortality; Brain Neoplasms - therapy; CD8-Positive T-Lymphocytes - immunology; Disease Models, Animal; Female; Glioma - genetics; Glioma - pathology; Humans; Immunotherapy; Immunotherapy, Active; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - immunology; Interleukin-12 - immunology; Medical sciences; Mice; Mice, Nude; Mice, SCID; Neoplasm Transplantation; Pharmacology. Drug treatments; T-Lymphocyte Subsets - immunology; T-Lymphocytes - physiology; T-Lymphocytes, Cytotoxic - immunology; Transfection; Tumor Cells, Cultured; Antineoplastic agent; Animal model; Cellular immunity; Malignant glioma; Transfection; Gene; Malignant astrocytoma; Immunotherapy; Established cell line; Intracranial; Nervous system diseases; Immunoglobulins; Immune response; Intercellular adhesion molecule 1; Cytokine; Rodentia; Cell adhesion molecule; Interleukin 12; Vaccine; Malignant tumor; Costimulatory molecule; Cerebral disorder; Genetic transfer; Vertebrata; Mammalia; Treatment; Mouse; Animal; Central nervous system disease; Genetic engineering
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19990827)82:5<714::AID-IJC15>3.0.CO;2-Q

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. Int. J. Cancer 82:714–720, 1999. © 1999 Wiley‐Liss, Inc.