Towards antibody-based immunotherapy development for platinum-resistant high-grade serous ovarian cancer.

Epithelial ovarian cancer is the sixth most common malignant neoplasm in women and the leading cause of death from gynecological malignancies in the Western World. The five-year survival rate is 45-48% because of the high frequency of late-stage diagnoses and the development of chemo-resistant disease. To assess the potential of antibodies and complement to kill platinum (Pt)-resistant and Pt-sensitive cell lines, antibodies S2 and Yth53.1 were tested at varying concentrations using high-grade serous ovarian cancer (HGSOC) cells. Cell lysis was quantified after 60 minutes using the impermeant dyes 7-Aminoactinomycin D and Annexin V. The cytotoxic effect of S2 was demonstrated through the activation of the complement and Yth53.1 monoclonal antibody neutralized the membrane attack complex (MAC) inhibitor CD59 and allowed assembly of the MAC. In contrast to Pt-based therapy, we found no evidence that chemo-resistance plays an important role when considering the antibody based therapy for Pt-resistant HGSOC cell lines. Significant killing efficiencies were achieved using antibodies against breast cancer cells (S2) and antibody against CD59 (Yht53.1) regardless whether the cell lines HGSOC (OVCAR-3, OVCAR-8) or CRISPR-Cas9 BRCA2 deleted OVCAR-4 were homologous recombination (HR) deficient or proficient, Pt sensitive or resistant. This work shows a potential towards antibody-based therapy development for Pt-resistant HGSOC.