A novel monoclonal antibody to the HLA of cisplatin resistant ovarian cancer cells (TUM2P.1018)

Abstract

Abstract Cisplatin is widely used as a chemotherapeutic drug in the treatment of ovarian cancer. Resistance to cisplatin occurs in about one-third of women during the primary course of treatment. We hypothesized that the class I HLA of cisplatin-resistant ovarian cancer cells present peptides distinct to these cells as compared to sensitive cells and that HLA/peptide complexes unique to cisplatin-resistant cells would be valuable targets for immunotherapeutic intervention. To identify the peptides that are uniquely presented by cisplatin-resistant ovarian cancer cells, the intrinsic cisplatin-resistant cells (SKOV3) and sensitive cells (A2780, OV90, FHIOSE) were characterized by comparative mass spectrometry. Peptide sequences distinct to cisplatin-resistant cells include a peptide (VMF11) derived from thioredoxin interacting protein (TXNIP) that was in high abundance in SKOV3. Next a T cell receptor mimic monoclonal antibody (RL41A) against A*02:01/VMF11 complex was generated. The specificity and affinity of RL41A toward VMF11/A*02:01 complex was shown by staining peptide-pulsed T2 cells and surface plasmon resonance respectively. Staining of ovarian cancer cells by flow cytometry also demonstrates that RL41A stains cisplatin-resistant cells but not drug sensitive cells. We therefore report the successful development of a monoclonal antibody that represents an attractive candidate for further validation using cisplatin-resistant and sensitive primary ovary tissues.