CAR T Cells Targeting MISIIR for the Treatment of Ovarian Cancer and Other Gynecologic Malignancies

Area of Science:

• Gynecologic Oncology
• Immunotherapy
• Cancer Biology

Background:

• Advanced ovarian and endometrial cancers have poor prognoses with limited treatment options.
• The Müllerian inhibiting substance type 2 receptor (MISIIR) is overexpressed in most ovarian and endometrial cancers but not in normal tissues.
• MISIIR ligation induces apoptosis in cancer cells, making it a potential therapeutic target.

Purpose of the Study:

• To develop and evaluate a chimeric antigen receptor (CAR) T-cell therapy targeting MISIIR for gynecologic malignancies.
• To assess the efficacy and specificity of MISIIR-targeted CAR T-cells against ovarian and endometrial cancers.

Main Methods:

• Development of a novel CAR construct targeting MISIIR.
• In vitro evaluation of CAR T-cell reactivity against cancer cell lines and patient-derived tumors.
• In vivo assessment of CAR T-cell efficacy in eliminating MISIIR-overexpressing tumors.
• Testing for cytotoxicity against normal primary human cells.

Main Results:

• MISIIR-specific CAR T-cells exhibited antigen-specific reactivity in vitro.
• CAR T-cells effectively eliminated MISIIR-overexpressing tumors in vivo.
• MISIIR CAR T-cells recognized and lysed various human ovarian and endometrial cancer cell lines and patient-derived specimens.
• No significant cytotoxicity was observed against normal primary human cells.

Conclusions:

• CAR T-cell technology is a viable approach for targeting MISIIR in ovarian cancer and other gynecologic malignancies.
• MISIIR-targeted CAR T-cells demonstrate potent and specific anti-tumor activity against relevant cancer types.
• This strategy offers a promising new avenue for treating advanced gynecologic cancers.