Ovarian cancer is responsible for the highest mortality rate among patients with gynecologic
malignancies. Therefore, there is an emerging need for
innovative therapies for the control of advanced
ovarian cancer.
Immunotherapy has emerged as a potentially plausible approach for the control of
ovarian cancer. In the current study, we have generated
heat shock protein 70 (Hsp70)-secreting murine
ovarian cancer cells that express
luciferase (MOSEC/luc). Hsp70 has been shown to target and concentrate antigenic
peptides in dendritic cells and is also able to activate dendritic cells. We characterized the
antigen-specific immune response and the antitumor effect of the MOSEC/luc cells expressing Hsp70 using noninvasive luminescence images to measure the amount of ovarian
tumors in the peritoneal cavity of mice. We found that mice challenged with MOSEC/luc cells expressing Hsp70 generate significant
antigen-specific CD8+ T-cell immune responses. Furthermore, we also found that mice vaccinated with irradiated MOSEC/luc cells expressing Hsp70 generate significant
therapeutic effect against MOSEC/luc cells. In addition, we have shown that CD8+, natural killer, and CD4+ cells are important for protective antitumor effect generated by irradiated
tumor cell-based
vaccines expressing Hsp70. Moreover, we also found that CD40 receptor is most important, followed by
Toll-like receptor 4 receptor, for inhibiting in vivo
tumor growth of the viable MOSEC/luc expressing Hsp70. Thus, the use of Hsp70-secreting ovarian
tumor cells represents a potentially effective
therapy for the control of lethal
ovarian cancer.