Abstract 1459: The immuno-AVI-PDX, am innovative patient-derived xenograft model for preclinical immuno-oncology studies

Abstract

Abstract Over the last decade, the success of immunotherapy in treating numerous solid and hematological tumors is unprecedent. However, the poor preclinical predictive power of current model systems explains in part the failures during late-stages clinical drug development for the numerous potential immunotherapies. Thus, there is a crucial need for innovative technologies offering fast and reliable evaluation of immunotherapies on patient-derived models. Using its proprietary process of micro-implantation of patient tumor cells within selected organs of series of avian embryos, Oncofactory developed two humanized avian xenograft models, namely IMMUNO-AVI-patient derived xenograft (iAVI-PDXTM) and IMMUNO-AVI-cell line derived xenograft (iAVI-cellDXTM). These models, consisting in the co-implantation of human peripheral-blood mononuclear cells (PBMC) and human cancer cells were validated through a sequence of experimental steps. First, we found that transplantation of PBMCs into avian tissues exhibited good survival and low allogenicity against the avian embryonic organism. Second, in embryos engrafted with tumoral cells, we established that intravenously injected PBMCs successfully populated the tumor. Third, to reduce the dilution of immune cells in the embryonic tissues and to better standardize the number of implanted cells in between embryos, we optimized the process by direct co-implantation of both PBMCs and cancer cells. We analyzed the immune cell contingent sorted from dissected tumors and found that all major immune cells populations, including T and B lymphocytes, monocytes as well as NK cells were preserved post-grafting, when compared to pre-grafted PBMCs. The AVI-cellDXTM and AVI-PDXTM models initially developed by Oncofactory allows fast and reproducible tumor growth with statistical evaluation of molecule efficacy already at 24 hours post-injection. To assess whether our humanized models retain these advantages, we analyzed the outcome of anti-PD1 antibody (Pembrolizumab) intravenous injection in series of avian embryos co-engrafted with human PBMCs and PDL1-expressing breast and colorectal cancer cell lines. Twenty-four hours post vehicle or Pembrolizumab exposure, we analyzed the tumor volumes in grafted embryos using light sheet microscopy. In all three cancer models, we found a statistically significant reduction of the volume upon pembrolizumab, compared with vehicle. Using a panel of molecular markers in flow cytometry, we found that the Pembrolizumab efficiently targeted T lymphocytes in the tumors. Finally, we validated the efficiency of Pembrolizumab treatment in models of co-implantation of human PBMCs with melanoma and colorectal patient samples. Thus, humanized iAVI-cellDXTM or -PDXTM technology bring powerful and fast alternative to mouse models, to strongly accelerate preclinical developments in immuno-oncology. Citation Format: Marjorie Lacourrege, Clélia Costechareyre, Loraine Jarrosson, Romain Teinturier, Frédéric Berget, Céline Delloye-Bourgeois, Valérie Castellani. The immuno-AVI-PDX, am innovative patient-derived xenograft model for preclinical immuno-oncology studies [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 1459.