Immunotherapy of ovarian cancer

PhD ceremony: Ms. R. Vermeij, 16.15 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Immunotherapy of ovarian cancer

Promotor(s): prof. H.W. Nijman, prof. C.A.H.H. Daemen

Faculty: Medical Sciences

Because patients with epithelial ovarian cancer (EOC) have a poor prognosis, new therapeutic strategies are urgently needed. The prognosis of EOC patients is influenced by tumor infiltrating immune effector cells, which makes an immunotherapeutic approach promising. In EOC, vaccines can induce antigen-specific immunity, but substantial clinical efficacy has not been observed. These disappointing clinical results were explained by immune escape mechanisms of tumor cells. Future therapeutic strategies may focus on combined approaches which are designed to restore antitumor immune responses.

This thesis deals with antigen-specific immunotherapy for treatment of patients with EOC, and combination strategies to augment its function. We conclude that the p53-SLP vaccine is a promising cancer vaccine as it is able to induce both short-term and long-term p53-specific immunity. Moreover, cyclophosphamide is a promising agent to potentiate the p53-SLP vaccine in recurrent ovarian cancer patients. Potential approaches to augment the immunogenicity and clinical effect of a p53-vaccine are the addition of other antigens such as SP17, NY-ESO-1, WT1 and survivin. WT1 could also be targeted alone, if combined with Treg depletion and up-regulation of MHC class I. The majority of advanced EOC patients have PD-L1 and/or PD-L2 expression; however, PD-L1 and PD-L2 have no (negative) effect on prognosis.