RANTES Secretion by Gene-Modified Tumor Cells Results in Loss of Tumorigenicity In Vivo: Role of Immune Cell Subpopulations

Overview summary Members of the chemokine superfamily mediate potent and selective chemoattraction of a variety of immune cell subsets, which is concentration dependent. This important and novel biologic activity raises the possibility of using chemokines as adjuvants in cancer vaccine strategies. We describe here the in vitro chemotactic capacity of RANTES for murine CD8+ tumor-infiltrating lymphocytes (TIL). Moreover, murine fibrosarcoma cells transfected with the cDNA encoding RANTES and secreting high levels of this chemokine become nontumorigenic in immunocompetent mice. The antitumor effect of RANTES is dependent on inherent tumor immunogenicity and is mediated through the participation of host-derived T cells and macrophages. Thus, the general chemoattractant properties exhibited by RANTES in vitro appear to be relevant in an in vivo model. These data warrant further investigation of other distinct members of the chemokine superfamily for their potential use, either alone or in combination, in gene therapy approaches that employ tumor cells as immunogens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63285/1/hum.1996.7.13-1545.pd