Oregovomab Plus Chemo in Newly Diagnosed Patients with Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery (FLORA-5/GOG-3035)

Gregory, Stephanie N; Sarvestani, Amber Leila; Ryan, Carrie E; Teke, Martha E.; Akmal, Sarfraz R; Hernandez, Jonathan M.; Gupta, Sunil

doi:10.1245/s10434-022-12838-w

Cited by 3 publications

(1 citation statement)

References 9 publications

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“…Cancer treatments for MUC16 cancers are currently at various stages of progress. For example, clinical trials for the targeted monoclonal antibody drug Oregovomab and CAR T therapy (JCAR-020) for MUC16 are in progress [ 16 , 17 ]. Furthermore, there are several drugs in development that target MUC16, such as bispecific T-cell engagers (BiTE) and antibody–drug conjugates (ADC) [ 9 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Mesothelin-based CAR-T cells exhibit potent antitumor activity against ovarian cancer

Guo,

Zeng,

Zhu

et al. 2024

J Transl Med

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Background Ovarian cancer (OC) is characterized by its rapid growth and spread which, accompanied by a low 5-year survival rate, necessitates the development of improved treatments. In ovarian cancer, the selective overexpression of Mucin-16 (MUC16, CA125) in tumor cells highlights its potential as a promising target for developing anti-tumor therapies. However, the potential effectiveness of CAR-T cell therapy that targets MUC16 in ovarian cancer cells is unknown. Methods The expression of MUC16 in viable OC cells was detected using immunofluorescence and flow cytometry techniques. A MSLN-CAR construct, comprising the MUC16-binding polypeptide region of mesothelin (MSLN), a CD8 hinge spacer and transmembrane domain, 4-1BB, and CD3ζ endo-domains; was synthesized and introduced into T cells using lentiviral particles. The cytotoxicity of the resultant CAR-T cells was evaluated in vitro using luciferase assays. Cytokine release by CAR-T cells was measured using enzyme-linked immunosorbent assays. The anti-tumor efficacy of the CAR-T cells was subsequently assessed in mice through both systemic and local administration protocols. Results MSLN-CAR T cells exhibited potent cytotoxicity towards OVCAR3 cells and their stem-like cells that express high levels of MUC16. Also, MSLN-CAR T cells were inefficient at killing SKOV3 cells that express low levels of MUC16, but were potently cytotoxic to such cells overexpressing MUC16. Moreover, MSLN-CAR T cells delivered via tail vein or peritoneal injection could shrink OVCAR3 xenograft tumors in vivo, with sustained remission observed following peritoneal delivery of MSLN-CAR T cells. Conclusions Collectively, these results suggested that MSLN-CAR T cells could potently eliminate MUC16- positive ovarian cancer tumor cells both in vitro and in vivo, thereby providing a promising therapeutic intervention for MUC16-positive patients.

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