Abstract LB031: A modular framework for cell and gene therapy assessment in preclinical mouse models

Abstract

The development of cell and gene therapies (CGTs) and biologics relies on designing custom preclinical strategies that provide high-confidence data using predictive animal models. To help investigators navigate navigating the increasingly complex and customizable preclinical landscape, we present a modular design framework for the preclinical evaluation of oncology therapies using traditional and next-generation mouse models. This guide illustrates how investigational requirements specific to each therapeutic candidate influence the selection of model features, including tumor characteristics (such as indication, markers, and engraftment site), immune system status (immunodeficient, immunocompetent, humanized), and compatible readouts. Through a series of proof-of-concept studies, we demonstrate optimal strategies for evaluating persistence, biodistribution, efficacy, safety, and in vivo mechanisms of action of various CGTs such as extracellular vesicles, CAR-NKs, TCR-Ts, and CAR-Ts in autologous and allogeneic settings. The dissemination of such expertise-based frameworks coupled with the increased availability and affordability of custom and/or humanized immune system mice, is poised to mitigate drug candidate attrition in oncology clinical trials. Modularity of the disease feature in this framework, e.g. swapping the tumor for infectious or inflammatory agent, further expands it impact to immuno-inflammatory and infectious disease areas. Citation Format: Emilie Bayon, Pierre Wallet, Joséphine Zangari, Iris Nkamba, Sébastien Tabruyn, Dan Georgess. A modular framework for cell and gene therapy assessment in preclinical mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited s); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2): nr LB031.