Cancer Testis Antigen Vaccination Affords Long-Term Protection in a Murine Model of Ovarian Cancer

Abstract

Sperm protein (Sp17) is an attractive target for ovarian cancer (OC) vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17) was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.

Mapping T and B cell epitopes in sperm protein 17 to support the development of an ovarian cancer vaccine

“…Regardless of the mechanism, the induction of protection against a single epitope is worthy of exploration for vaccine development, since as well as useful by itself, it could be combined with other peptide epitopes, to broaden reactivity and overcome the potential for immune evasion. In this context it will also be of interest to confirm in future studies whether Sp17 has a critical or non-redundant role in OC, and hence could be used as a stand-alone antigen in a vaccine, as suggested previously [23,29,45,46]. Since, Sp17 was also identified as a candidate gene related to the chemo-resistance to paclitaxel of clear cell carcinoma [47], vaccines that target Sp17 could also have unique potential to enhance the effectiveness of standard first-line OC chemotherapy.…”

“…as described in Chiriva's study [29]. In the positive control formulation (rmSp17 + CpG), despite positive IFN-␥ responses being detected upon stimulation with rmSp17 protein by IFN-␥ ELISPOT assay (Fig.…”

“…Full length rmSp17 protein adjuvanted by CpG has been shown to be protective and provided therapeutic efficacy after 9 repeated immunisations in C57BL/6 mice [29]. Efficacy was suggested in these studies to be mediated by either CD8+ T cells or Th17 cells.…”

“…Chiriva et al [29] showed that CpG-adjuvated Sp17 vaccines have both therapeutic and prophylactic activity in the C57BL/6-ID8 syngeneic murine model of OC. In that study, recombinant Sp17 increased overall levels of CTL responses, suggesting antigen specific responses had been induced, though it was not formally demonstrated and no specific CD8 T cell epitopes were mapped.…”

Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis

“…Here, we propose a different model in which Notch signaling and CTA expression interact to maintain a self-replicating MM cell population. Although CTA expression has been described in a broad range of solid and hematologic malignancies [33,35,36,39,40,41,43], MM is distinct in that a significant majority of patients express AKAP-4 and/or SP17 in their tumor cells [34,37,38,42]. No other type of cancer has such a close association with specific CTA expression pattern.…”