NSCLC patient-derived xenografts perpetuating tumor-associated, tumor-reactive T cells that respond to immunotherapy but do not cause GVHD in host mice
نویسندگان
چکیده
Abstract Non-small cell lung cancer (NSCLC) is the leading cause of malignancy-related deaths worldwide. We wished to overcome a current major limitation PDX modeling, by providing autologous human T cells suitable for immunotherapy responses, but notably, without graft versus host disease (GVHD). have developed PDXs from NSCLC implanting surgically resected patient tumors subcutaneously in NOD scid gamma (NSG) mice. used metastatic model test potential therapeutic efficacy novel molecule, anti-human-CD3ɛ monovalent Fab fragment (Mono-OKT3-Fab) and compared tumor growth results with anti-human PD-L1 therapy. Overall engraftment rate unique, primary was 52%. Over multiple passages vivo, retained expression tumor-matched NSCLC-diagnostic pathological markers. Moreover, primary-tumor-associated were present passaged mice producing any signs GVHD. Immunotherapy showed significant response PDL-1+ tumor, consistent functional tumor-specific passaging our system. In contrast, control experiments using patient-matched PBMCs vigorous GVHD presence or absence co-transplanted tumor; this demonstrated that non-tumor-associated lymphocytes these patients capable xenoreaction, even though tumor-associated not. observed PDX-NSG treated either modality significantly reduced burden increased survival over control-Ig-treated Overall, study shows implanted NSG resected-NSCLC retain sufficient preclinical evaluation cell-targeting immunotherapies. NIH, National Cancer Institute, IOTN(U01 CA244314) NIAID, R01 AI097187 Mizzou Start-up funds
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.230.12