An antibody–drug conjugate for endometrioid carcinoma based on the expression of cell adhesion molecule 1

Abstract

Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1–targeting antibody–drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1–MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1–MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1–MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.

Keywords

• CADM1
• early-stage cancer
• endometrial hyperplasia
• fertility preservation
• gynecologic oncology