Integrin Inhibitor Under Study as Targeted Therapy for Ovarian Cancer
Posted: Wednesday, September 30, 2020
Research has shown that approximately 80% of patients with ovarian cancer respond to typical first‐line chemotherapy treatments, but more than 70% experience disease recurrence and treatment resistance within 5 years. In early preclinical research published in Cancer Science, a team of researchers sought to identify ovarian cancer–specific antibodies that may improve treatment outcomes for these patients. After screening several monoclonal antibodies, they found one with therapeutic potential in ovarian cancer: integrin α3 (ITGA3).
Han-Chung Wu, PhD, of Academia Sinica, Taipei, Taiwan, and colleagues stated: “Because antibodies have high specificity for their target antigens, monoclonal antibody therapeutics often cause fewer adverse effects in patients compared with traditional chemotherapy. Moreover, antibodies that specifically recognize ovarian cancer cells may be useful in diagnostic and/or therapeutic applications.”
To generate monoclonal antibodies against ovarian cancer, mice were immunized with live, human ovarian carcinoma cells. After incubation, cells were harvested and grown to produce hybridoma clones, which were screened to identify monoclonal antibodies.
Results revealed 30 monoclonal antibodies with no cross-reactivity to normal cells. Furthermore, one antibody (OV‐Ab 30‐7) was revealed to target ITGA3, a gene linked to poor prognosis if elevated in ovarian cancer. This antibody was also found to regulate p21 and p53, genes known to induce apoptosis in cancer cells.
To assess its antitumor efficacy, researchers treated tumor-bearing mice with the monoclonal antibody alone or in combination with carboplatin and paclitaxel. The results revealed prolonged survival and inhibited tumor progression in mice treated with the antibody alone (P < .01), as well as in mice treated with the chemotherapy/antibody combination (P < .05). Based on their findings, Dr. Wu and colleagues concluded: “Our study introduces integrin α3 as a potential therapeutic target in ovarian cancer and provides a novel biologic drug candidate for this purpose.”
Disclosure: The study authors reported no conflicts of interest.