Vaccination with IL-18 gene-modified, superantigen-coated tumor cells elicits potent antitumor immune response

Abstract.

Objective: To investigate the induction of antitumor immune response by vaccination with interleukin-18 (IL-18) gene-modified, C215Fab-SEA-coated tumor cells. Materials: A B16-C215 cell clone stably expressing C215 antigen was established by transfecting the gene-encoding C215 antigen into B16 melanoma cells. The manipulated tumor cell vaccine was prepared with B16-C215 cells genetically modified with the IL-18 gene, coated with the fusion protein of SEA and the Fab region of C215 mAb (C215Fab-SEA) which specifically binds to the C215 antigen and then irradiated. C57BL/6 mice were vaccinated with IL-18 gene-modified, C215Fab-SEA-coated B16-C215 cells followed by tumor challenge. Tumor growth and survival time were observed. The expansion of CD4⁺, CD8⁺ cells in lymphocytes derived from draining lymph node was detected by FACS. Induction of CTL activity by vaccination was measured by ⁵¹Cr release assay. Results: IL-18 gene-modified, C215Fab-SEA-coated B16-C215 cell vaccine effectively stimulated lymphocyte proliferation and CD4⁺, CD8⁺ cell expansion in vitro. It was more immunogenic than B16-C215 cells genetically modified with IL-18 gene alone or B16-C215 cells coated with C215Fab-SEA alone. Immunization of the mice with the manipulated vaccine elicited protective immunity against the following tumor challenge of parental B16-C215 and wild-type B16 cells. Significant expansion of CD4⁺, CD8⁺ T cells was observed in the draining lymph node of the immunized mice when compared with that in unvaccinated mice. Higher CTL activity was induced in vaccinated mice than that in unvaccinated mice. Conclusion: Vaccination with IL-18 gene-modified, C215Fab-SEA-coated tumor cells elicited potent antitumor response through induction of tumor-specific immune response.