Vaccine therapy for murine glioma using tumor cells genetically modified to express B7.1.
OBJECTIVE
In a syngeneic mouse brain tumor model, we tested the hypothesis that vaccination with tumor cells genetically modified to express B7.1 molecules induces tumor-specific T cells and immunological antitumor effects.


METHODS
Malignant glioma cells (RSV-MG) derived from a C3H/He mouse induced by Schmidt-Ruppin Rous sarcoma virus (RSV) were infected with an adenovirus encoding the B7.1 gene (AdB7). To investigate the effects of B7.1 expression on the tumorigenicity of RSV-MG cells, infected cells were implanted subcutaneously into C3H/He mice. The C3H/He mice were vaccinated with AdB7 transfectants injected subcutaneously and 2 weeks later were challenged intracerebrally with wild-type RSV-MG cells to determine whether or not the expression of B7.1 would enhance the immunogenicity of RSV-MG cells.


RESULTS
Immunocytochemistry confirmed the expression of B7.1 and major histocompatibility complex Class I antigen on the infected cells. The growth of subcutaneous tumors was markedly retarded in the AdB7 group, whereas tumors had formed and progressively increased in size in the other control groups. In the vaccine experiments, the mice immunized with AdB7 transfectants survived longer than did the mice of the other groups, and a significant difference in survival times was noted. Immunocytochemistry revealed that brain tumors in mice previously vaccinated with AdB7 infectants had been infiltrated by a larger number of CD3(+) lymphocytes and that these CD3(+) lymphocytes contained not only CD4(+) and CD8(+) T cells but also CD25(+)-activated T cells. In addition, a cytotoxicity assay confirmed that vaccination with the AdB7 transfectants induced tumor-specific cytotoxicity.


CONCLUSIONS
These results demonstrate the therapeutic potential of vaccination with tumor cells expressing B7.1 for the treatment of malignant glioma.
Morioka
Jun
J
Department of Neurosurgery, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Kajiwara
Koji
K
Yoshikawa
Koichi
K
Ideguchi
Makoto
M
Uchida
Tetsuya
T
Suzuki
Michiyasu
M
D000256:Adenoviridae; D000818:Animals; D001358:Avian Sarcoma Viruses; D018122:B7-1 Antigen / Q000008:administration & dosage* / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000821:virology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005910:Glioma / Q000188:drug therapy* / Q000821:virology; D016233:Immunotherapy, Active / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H
D018122:B7-1 Antigen