MtHsp70-CLIC1-pulsed dendritic cells enhance the immune response against ovarian cancer

Abstract

Approximately 80% of ovarian cancer (OC) is diagnosed at late stages, and most patients die within 5 years of diagnosis due to recurrence or drug resistance. Novel treatments are required to improve patient survival. Immune therapy against cancer is promising; however, therapeutic vaccination has been limited by the inability of tumor antigens to induce effective immune responses. Chloride intracellular channel 1 (CLIC1) was previously identified as a possible tumor marker for OC. In this study, we constructed a recombinant protein by conjugating the extracellular domain of CLIC1 to the carboxyl terminus of Mycobacterium tuberculosis heat shock protein 70 (MtHsp70). Human dendritic cells (DCs) derived from cortical blood were pulsed with the fusion protein, and the antitumor effect of human cytotoxic T lymphocytes (CTLs) stimulated by autologous DCs was assessed in NOG mice. MtHsp70-CLIC1 promoted the phenotypic maturation of human DCs and the secretion of Th1-associated cytokines in vitro. MtHsp70-CLIC1-stimulated CTLs generated a CLIC1-specific immune response both in vitro and in vivo. These results indicate that DCs pulsed with MtHsp70-CLIC1 can enhance antitumor immunity against OC, providing a novel immune therapeutic strategy.

Keywords: Chloride intracellular channel 1; Dendritic cell; Immune therapy; NOG mice; Ovarian cancer; Recombinant protein.