Abstract 1294: Primed human immune cell and cancer cell co-inoculated model for immuno-oncology drugs evaluation

Systemic peripheral blood mononuclear cell (PBMC) humanized model is a straightforward tool to evaluate therapeutic immuno-oncology (IO) drugs, including immune checkpoint blockers (ICB) and bispecific antibodies (BsAb). However, the model has a limited dosing regimen window due to graft-versus-host disease (GVHD), as seen in most immune deficient recipients. There is also a relative lower responsible rate from insufficient antigen specific immune cells infiltration into tumor microenvironment (TME). Thus, application of this PBMC humanized model is restricted in evaluation of multiple ICBs and myeloid cell- or lymphocyte-mediated BsAbs. To overcome this, LIDE has developed a unique co-inoculation model with primed human PBMC (or/and its derived immune cell subsets) and cancer cells. Cancer-priming human PBMCs are well mixed with fresh cancer cells in MatriGel, co-inoculated into immune deficient mice to form an immune cell relatively warm tumor tissue for late immunotherapy. This model can significantly delay the graft-versus-host-reaction for another month compared with traditional systemic PBMC humanized model, and achieves maximal therapeutic effect of the testing drugs by pre-activating T cells with specific tumor antigens. Considering minimum innate immune cells in TME, dendritic cells or macrophages are expanded ex vivo, then transferred into this co-inoculated system to work together with T cells with a proper survival rate in the dosing period, mimic clinical biopsy complexity, to help determine the overall effect induced by integrated signals. It seems CD40 agonist or CD47 antagonist could well synergize with anti-PD(L)1 to control melanoma and triple negative breast cancer development, respectively. This optimized immune cell humanized cancer-bearing mice models have been tested for various cancer targets, e.g., PD(L)1, Tim3, Lag3, Tigit, PVRIG, TGFβ1, CD73/CD39, CD47/Sirpa, DLL3/CD3, Claudin18.2/4-1BB/CD3, B7H3/CD3/ADC, GPC3/CD3, GPRC5D/CD3, CSF1R, GITR, (Pro)IL2/IL15, to better understand the interaction and modulation between cancer cells and immune cells. Citation Format: Bin Xie,Xin Hou,Pengfei Yang,Yanbing Zhou,Loc Van,Diandong Jiang,Josh Caggiula,Danyi Wen. Primed human immune cell and cancer cell co-inoculated model for immuno-oncology drugs evaluation [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 1294.