Abstract LB168: Advancing cancer therapy: Evaluating ADCC with R3CE-derived organoids

Abstract Antibody drugs have drawn significant attention due to their specific and dramatic therapeutic effects for cancer treatment in the past few years. For instance, the HER2-targeted monoclonal antibodies, trastuzumab, and pertuzumab, have been shown to improve survival rates in breast cancer patients with HER2-positive expression. Similarly, an alternative anti-EGFR monoclonal antibody, cetuximab, has been proven to be effective in the treatment of head and neck squamous cell carcinoma as well as in colorectal cancer patients. Mechanistically, the cytotoxic effects of these antibody drugs are at least partially mediated by the antibody-dependent cell-mediated cytotoxicity (ADCC) through immune cells. Recently, modifying the structure of antibodies has emerged as a promising strategy to enhance the affinity between the antibody and target protein. Meanwhile, a suitable assay platform to determine the therapeutic efficacy of these modified antibodies is under extensive investigation. Thus, a robust cell-based model that can be used to evaluate the efficacy of these antibodies for personalized medicine will further accelerate the development of antibody drugs. Here, we expanded and maintained the breast patient-derived organoids (PDOs) with varying levels of HER2 expression through the R3CE culture platform (AcroCyte Therapeutics) to assess the ADCC effects of natural killer (NK) cells ex vivo. By co-culturing NK cells and breast PDOs with trastuzumab, we observed highly positive correlation between the NK cell-to-PDO cytotoxicity with the levels of HER2 expression. The results demonstrated a reliable ex vivo model platform that could be used to evaluate ADCC relevant cytotoxicity for personalized applications and future therapeutic developments. Citation Format: Wen-Hung Kuo, Hao-Wei Han, Jia-Yang Chen, Chia-Chun Liu, King-Jen Chang, Ying-Chih Chang. Advancing cancer therapy: Evaluating ADCC with R3CE-derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB168.