The cellular immunotherapy field has achieved important milestones in the last 30 years towards the treatment of a variety of cancers due to improvements in ex-vivo T cell manufacturing processes, the invention of synthetic T cell receptors, and advances in cellular engineering. Here, we discuss major preclinical models that have been useful for the validation of chimeric antigen receptor (CAR)-T cell therapies and also promising new models that will fuel future investigations towards success. However, multiple unanswered questions in the CAR-T cell field remain to be addressed that will require innovative preclinical models. Key challenges facing the field include premature immune rejection of universal CAR-T cells and the immune suppressive tumor microenvironment. Immune competent models that accurately recapitulate tumor heterogeneity, the hostile tumor microenvironment, and barriers to CAR-T cell homing, toxicity, and persistence are needed for further advancement of the field.

中文翻译：

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保持发动机运转：临床前模型对CAR-T细胞发育的相关性和预测价值。

在过去的30年中，由于体外T细胞制造工艺的改进，合成T细胞受体的发明以及细胞工程的发展，细胞免疫治疗领域在治疗各种癌症方面已取得了重要的里程碑。在这里，我们讨论了主要的临床前模型，这些模型对于验证嵌合抗原受体（CAR）-T细胞疗法非常有用，并且有望为将来成功进行研究提供新的模型。然而，在CAR-T细胞领域仍有许多未解决的问题需要解决，这将需要创新的临床前模型。该领域面临的关键挑战包括通用CAR-T细胞的过早免疫排斥和免疫抑制性肿瘤微环境。能够准确概括肿瘤异质性的免疫能力模型，