Anti-CD73 and anti-OX40 immunotherapy coupled with a novel biocompatible enzyme prodrug system for the treatment of recurrent, metastatic ovarian cancer.
Approximately 75% of ovarian cancer is diagnosed once metastasis to the peritoneal cavity has occurred. A large proportion of patients eventually develop platinum-resistive tumors, which are considered terminal. In order to provide an alternative a novel fusion protein, mCTH-ANXA5, has been developed for the treatment of recurrent, metastatic ovarian cancer. The fusion protein combines annexin V (ANXA5), an ovarian tumor and tumor vasculature targeting protein, with mutated cystathionine gamma-lyase (mCTH), an enzyme that converts selenomethionine (SeMet) into toxic methylselenol, which generates reactive oxygen species and eventual tumor cell death. In order to further enhance the therapeutic efficacy, anti-CD73 and anti-OX40 immunostimulants were combined with mCTH-ANXA5, resulting in an increase of survival by 100% from 12 to 24 days post-therapy and decrease tumor burden in mice with orthotopic metastatic ovarian cancer. Further evaluation of the combination therapy revealed a strong antibody-mediated immune response, and an increased infiltration of cytotoxic T-cells along with a decrease in tumor promoting immune cells. This study demonstrates the efficacy of a synergistic, multi-drug system by attacking the tumor as well as enlisting the body's own defense system to treat the patient.
['Virani|Needa A|NA|', 'Thavathiru|Elangovan|E|', 'McKernan|Patrick|P|', 'Moore|Kathleen|K|', 'Benbrook|Doris M|DM|', 'Harrison|Roger G|RG|']
D015720:5'-Nucleotidase D000818:Animals D017304:Annexin A5 D000906:Antibodies D000971:Antineoplastic Combined Chemotherapy Protocols D045744:Cell Line, Tumor D003542:Cystathionine gamma-Lyase D004357:Drug Synergism D005260:Female D006801:Humans D007167:Immunotherapy D051379:Mice D009362:Neoplasm Metastasis D009364:Neoplasm Recurrence, Local D053278:OX40 Ligand D010051:Ovarian Neoplasms D011355:Prodrugs D011993:Recombinant Fusion Proteins D013602:T-Lymphocytes, Cytotoxic D023041:Xenograft Model Antitumor Assays
Anti-CD73 Anti-OX40 Enzyme prodrug Cancer Annexin V Phosphatidylserine