Abstract 6782: 3D-EXpress - an <i>ex vivo</i> platform using viably cryopreserved tumoroids for rapid assessment of targeted therapeutic outcomes
Authors: Vanessa Garrido, Michelle Ataya, Nisha R. Dhanushkodi, Seth Currlin, Alliyah Humphrey, Jared Ehrhart, Rikhia Chakraborty
Journal: Cancer Research (2024)

Abstract Background: it has been a significant challenge to select, combine, and sequence the multiple FDA-approved IO therapies and pharmaceutical agents, highlighting the need to develop a precision oncology platform to explore novel combination treatments. 3D-EXpress is a unique ex vivo therapeutics testing platform using a biorepository of fresh patient tumoroids that were never dissociated, propagated, or reassembled to retain an intact microenvironment. Therefore, these specimens provide an excellent ex vivo platform to investigate the efficacy of therapeutics targeting the tumor microenvironment. Here, we employed the 3D-EXpress platform to compare the efficacy of different therapeutic modalities targeting tumor antigens and immune checkpoint ex vivo. Methods: Tumoroids measuring 150 μm in size retaining tumor cell heterogeneity, tumor-resident immune cells, stromal components, and extracellular matrix interaction were prepared from human endometrial and colorectal tumors. Tumoroids were cryopreserved and were selected based on tumor antigen status. Samples were treated for 72 hours ex vivo with antibody-drug conjugates, chimeric antigen receptor (CAR)T cells, or bispecific antibodies alone and in combinations. Treatment-mediated changes in tumor cell killing and tumor immune microenvironment were investigated. Results: 3D high throughput confocal imaging and Nilogen Oncosystem’s proprietary algorithm were used to detect and analyze treatment-induced tumor cell killing activity in tumoroids. The impact of ex vivo treatment by different modalities in combination with chemotherapeutic agents upon tumor resident immune cell populations was monitored by deep immune phenotyping and multiplex cytokine release assay. Based on the ex vivo responses tumors were assigned to treatment sensitive and resistant groups. Correlative analysis was performed and compared with detailed clinicopathologic data that is readily available for Biorepository tumors. Conclusions: The 3D-EXpress platform using cryopreserved 3D tumoroids with intact tumor microenvironment is an effective tool for the pre-clinical assessment of rational drug combinations for treatment of solid tumors. Furthermore, the 3D-EXpress platform provides unique insight into the microenvironment of both treatment responsive and non-responsive tumors and can aid in the development of patient-centered therapeutic regimens. Citation Format: Vanessa Garrido, Michelle Ataya, Nisha R. Dhanushkodi, Seth Currlin, Alliyah Humphrey, Jared Ehrhart, Rikhia Chakraborty. 3D-EXpress - an ex vivo platform using viably cryopreserved tumoroids for rapid assessment of targeted therapeutic outcomes [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(6_Suppl):Abstract nr 6782.