Autologous Hsp70 immunization induces anti-tumor immunity and increases longevity and survival of tumor-bearing mice

Abstract

Heat Shock proteins 70 (Hsp70) is a family of highly conserved molecules that maintain the function of crucial cellular pathways during stress. Hsp70 derived from tumor cells is bound with tumor antigenic peptides from the diverse antigen cytosolic pool. Tumor-derived Hsp70 preparations after ex vivo administration permit antigen presenting cells (APCs) to present tumor antigen to their cell surface and induce tumor specific immunity in many types of malignancies by directly eliciting cytotoxic T lymphocytes (CTL) response. In the present investigation, we have demonstrated that immunization with tumor cell derived Hsp70 lead to an effective survival advantage in mice with minimal residual tumor cells from which Hsp70 is derived, by involvement of immune cell types in the rejection of tumor in the Hsp70 immunized tumor-bearing host mice and their post-immunization cytokine repertoire. It has been observed that autologous Hsp70 induces specific anti-tumor immunity and effectively eradicates tumors in the host mice, thereby enhancing survival of tumor-bearing host. Immunization with tumor-derived autologous Hsp70 effectively primed specific CTL response and increased tumor cell lysis independently of CD4 (+)T lymphocytes. Increase in type I cytokines in the serum of Hsp70 immunized mice was also observed that indicates its adjuvant property in the host. Furthermore, Hsp70 immunized mice did not show any systemic disorder. Therefore, it could be assumed as safe and might be clinically useful for vaccination against malignant human tumors.