Abstract 241: Patient-derived organoids as a reliable screening platform for assessing ADC efficacy and specificity

Abstract Antibody-drug conjugates (ADCs) are a new class of pharmaceutical drugs designed to deliver cytotoxic agents to cells expressing specific antigens selectively. Based on Paul Ehrlich’s “magic bullet” concept, ADCs are designed to target cancer cells, minimizing systemic toxicity typical of conventional chemotherapy. ADCs structurally consist of a particular monoclonal antibody linked to a cytotoxic agent. Patient-derived Organoids (PDOs) provide a new tool for studying cancer biology and patient stratification. PDOs are adult stem cell-based culture systems maintaining the patient-specific genetic and phenotypic characteristics, including surface marker expression. HUB Organoids has generated a large biobank of PDOs characterized on the genomic and transcriptomic level. The work presented here shows the suitability of the organoid platform for performing ADC screening. Organoids were selected based on their target-antigen (TA) expression, assessed by flow cytometry and RPKM. Organoid killing was assessed with a viability readout (CellTiter Glo) after six days of treatment. Results of viability screening show a correlation between TA-targeting ADC-induced organoid killing and TA expression in the organoids. These results reveal that PDOs hold value for the preclinical development of ADCs and for evaluating their tumor specificity. Moreover, PDOs have the potential to predict patient specific response to ADCs. Citation Format: Daniele Mori, Vineeta Adegbenro, Francisco Morales, René Overmeer, Sabina Lukovac, Sylvia Boj, Merel Derksen. Patient-derived organoids as a reliable screening platform for assessing ADC efficacy and specificity abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 241.