Crown Bioscience Inc., San Diego, California, USA.
Curr Protoc. 2023 Aug;3(8):e852. doi: 10.1002/cpz1.852.
Breakthroughs in cancer treatment with immunotherapeutics have provided long-term patient benefits for many different types of cancer. However, complete response is not achieved in many patients and tumor types, and the mechanisms underlying this lack of response are poorly understood. Despite this, numerous new targets, therapeutics, and drug combinations are being developed and tested in clinical trials. Preclinical models that recapitulate the complex human tumor microenvironment and the interplay between tumor and immune cells within the cancer-immunity cycle are needed to improve our understanding and screen new therapeutics for efficacy and safety/toxicity. Humanized mice, encompassing human tumors and human immune cells engrafted on immunodeficient mice, have been widely used for many years in immuno-oncology, with developments to improve both the humanization and the translational value central to the next generation of models. In this overview, we discuss recent advances in humanized models relevant to immuno-oncology drug discovery, the advantages and limitations of such models, the application of humanized models for efficacy and safety assessments of immunotherapeutics, and the potential opportunities. © 2023 Crown Bioscience. Current Protocols published by Wiley Periodicals LLC.
免疫疗法在癌症治疗方面的突破为许多不同类型的癌症患者带来了长期的益处。然而，许多患者和肿瘤类型并未获得完全缓解，其背后的机制也知之甚少。尽管如此，许多新的靶点、治疗方法和药物组合正在临床试验中得到开发和测试。需要能够重现复杂的人类肿瘤微环境以及癌症-免疫循环中肿瘤细胞和免疫细胞之间相互作用的临床前模型，以提高我们的理解，并筛选新的治疗方法的疗效和安全性/毒性。多年来，人源化小鼠（包含植入免疫缺陷小鼠的人类肿瘤和人类免疫细胞）已广泛应用于免疫肿瘤学领域，为提高模型的人源化程度和转化价值而进行的开发是下一代模型的核心。在这篇综述中，我们讨论了免疫肿瘤学药物发现相关的人源化模型的最新进展、这些模型的优缺点、人源化模型在免疫治疗药物的疗效和安全性评估中的应用，以及潜在的机会。© 2023 Crown Bioscience。Wiley Periodicals LLC 出版的《当代协议》。
