Abstract 7231: Immuno-oncology drugs fast in vivo efficacy test IO-FIVE for research and precision medicine
Authors: Bin Xie, Yang Liu, Yu Di, Xiaorong Gu, Kaimeng Hu, Song Xu, Loc Van, Josh Caggiula, Diandong Jiang, Danyi Wen
Journal: Cancer Research (2025)

Abstract Immunotherapy is becoming a promising cancer treatment for microsatellite-instability-high (MSI-H) pan-cancers, and combination therapy with IO drugs and anti-angiogenesis or antibody-drug-conjugates is considered as a first-line therapy for advanced or unresectable hepatocellular carcinoma and bladder cancer respectively. Though human CD34+HSC and PBMC humanized models are valuable tools to investigate the in vivo function and mechanism of immuno-oncology drugs, the allogeneic reaction between targeted cancer tissue and human immune system is a serious issue. Obviously, this could interfere with the fundamental reaction of the testing drugs particularly with mismatched HLA donors. Thus, there is an urgent and unmet need for a preclinical in vivo model that effectively mimics patients through autologous immune systems. LIDE’s Mini-PDX (mini-patient-derived xenografts) model has been widely applied to test the in vivo chemosensitivity of chemical and targeted compounds for more than 3000 clinical biopsies in the last decade. Leveraging this in vivo organoid system, we have developed the immuno-oncology version of MiniPDX, named “Immuno-Oncology drugs Fast In Vivo Efficacy” test or IO-FIVE. This assay uses patient cancer cells with its microenvironment immune cells and stroma cells isolated from the same fresh biopsy, well mixed and co-inoculated in mini-capsules before implantation into immune deficient mice. Total tissue viability and phenotyping of each cell subsets could be assessed within 2 weeks by Celltiter Glo and flow cytometry analysis respectively. Furthermore, omics study would shed new light for deeper understanding about the mechanism. Using this model, we found that Daratumumab (CD38-Ab) had a tumor suppression effect in less than half of CD38+ acute myeloid leukemia patients (response rate is around 30% in all AML N&amp;gt;60), and laboratory IO-FIVE data guided clinical Sintilimab (PD1-Ab), bevacizumab and capecitabine combo-therapy leads to a stable disease (SD) type for one advanced lung metastatic colon cancer patient with microsatellite stable genotype. Consistent to clinical trials, PD1 antibody (e.g., Sintilimab) monotherapy seems have limited tumor control effect in around one-fourth of ovarian cancer patients (N=11), IO and PARP inhibitor combo-therapy or novel drugs (bispecific antibody, ADCs) may enhance the immunotherapy efficiency and sensitivity. Our IO-FIVE model is offered as a unique in vivo functional assay to help do patient stratification as well as MOA studies. Citation Format: Bin Xie, Yang Liu, Yu Di, Xiaorong Gu, Kaimeng Hu, Song Xu, Loc Van, Josh Caggiula, Diandong Jiang, Danyi Wen. Immuno-oncology drugs fast in vivo efficacy test IO-FIVE for research and precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7231.