Near-Infrared Photoimmunotherapy Targeting Esophagogastric Junction Adenocarcinoma With Fully Human Anti-EpCAM Antibody.

Near-infrared photoimmunotherapy (NIR-PIT) is a tumor-specific treatment using monoclonal antibody (mAb) photosensitizer conjugates, followed by near-infrared light irradiation. This study aimed to identify the optimum target for treating esophagogastric junction (EGJ) adenocarcinoma and to evaluate the efficacy of NIR-PIT using mAbs in preclinical models. Tumor samples from 46 consecutive patients who had undergone surgery without any prior treatment for EGJ adenocarcinoma were assessed for expression and homogeneity of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and epithelial cell adhesion molecule (EpCAM) through immunohistochemistry. Results showed positive rates of 22%, 13%, and 98% for EGFR, HER2, and EpCAM, respectively, with EpCAM also demonstrating the highest homogeneity (93%). Therefore, EpCAM was selected as the optimal target for NIR-PIT. The fully human monoclonal antibody targeting EpCAM, adecatumumab, was conjugated with the photosensitizer IR700 at different dye-antibody ratios (DAR2, DAR4, DAR7) and tested on OE19 cells and xenograft mouse models under near-infrared light irradiation. NIR-PIT with adecatumumab-IR700 significantly reduced tumor size and improved prognoses compared to controls, with DAR2 showing the best balance of efficacy and minimal side effects. Notable EpCAM expression and homogeneity underpin EpCAM as a promising target for NIR-PIT in EGJ adenocarcinoma. The fully human anti-EpCAM antibody may be suitable for NIR-PIT in EGJ adenocarcinoma.