Abstract 5183: LGR5 CAR-T cells: A novel potential treatment against high grade serous ovarian cancer

Abstract

Abstract Ovarian cancer is second leading cause of cancer-related mortality among gynecological cancers in the Western world. Although initial responses to 1st line treatment is high, over 75% of patients eventually relapse and acquire chemotherapy resistance, which is the primary cause of ovarian cancer treatment failure. New therapies to improve patient outcome are therefore urgently required. Chimeric antigen receptor T (CAR-T) cell therapy is an adoptive immunotherapy that is currently being used to treat some blood cancers. CAR-T cell therapies have so far been less effective against solid cancers, due in part to the absence of suitable tumor-associated antigen (TAA).This study has investigated whether Leucine-rich repeat-containing G protein-coupled receptor 5, LGR5) is a suitable target for CAR-T cell therapy for ovarian cancer. We found that LGR5 is highly expressed in HGSOC cancer lines (COV318, COV362 and OAW28) and increased in HGSOC tissues following relapse with chemotherapy resistant disease. We assessed the cytotoxic effects of LGR5-CAR-T cells on a range of ovarian cancer cell lines and primary serous ovarian cancer cells derived from patient ascites in vitro by MTT and 3D spheroid assays. We demonstrated that LGR5-CAR-T cells were cytotoxic and significantly inhibited survival of ovarian cancer cell lines (COV318, COV362) that express high levels of LGR5 but not SKOV3 or OV90 that express lower LGR5 levels in monolayer culture. In addition, LGR5-CAR-T cells were cytotoxic and significantly inhibited survival of primary serous ovarian cancer cells compared to un-transduced CD3+ T cells. LGR5 CAR-T cells also exhibited anti-tumor activity against ovarian cancer cell lines (COV318, COV362 & OAW28) and primary serous ovarian cancer cells in vitro using 3D-spheroid culture assays. This study demonstrates that LGR5-CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer. Citation Format: Wanqi Wang, Veronika Bandara, Noor Lokman, Silvana Napoli, Batjargal Gundsambuu, Martin Oehler, Simon C. Barry, Carmela Ricciardelli. LGR5 CAR-T cells: A novel potential treatment against high grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5183.