In vitro andin vivo chemotactic effect of mip-lα gene transfected tumor vaccine on immune effector cells

Abstract

Vaccination with chemokine gene-transfected tumor cells may be a new apporach to cancer treatment. Macrohage inflammatory protein-la (MIP-lα ) is a new type of chemokines which has chemotactic activity on effector cells. In the present study, the B16 melanoma cells were transfected with recombinant adenovirus harboring murine MIP-1α gene. The biological characteristics of the MIP-lα gene transfected B16 melanoma cells were investigated. The level of MlP-lα in the supernatant of gene-transfected melanoma cells was 368±24 ng/ml/106/24hr. This supernatant showed strong chematactic activity for NK cells, CD4+ T cells, CD8+ T cells or the freshly isolated peritoneal macrophages. Though thein vitro growth were not altered, the tumorigenicity of the gene-transfected B16 melanoma cells decreased signicantly. The infiltration of inflammatory cells into the tumor mass formed by MIP-lα gene-transfected B16 cells were much more obvious than that by wild-type B16 cells or B16 cells transfected with the control gene. However, the survival time of the mice bearing B16 melanoma cells transfected with MIP-1 a gene was not prolonged and the NK, CTL activity remianed unchanged. We suggested that thein vivo phenomenon may be related to the high toxicity of the MIP-1 α as a strong non-specific inflam-matory mediator.