Clinical Research on T Cell Receptor-Engineered T Cells Therapy and Application of Its Preclinical Animal Models
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摘要: T细胞受体工程化T细胞(T cell receptor-engineered T cells,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)疗法是2种过继性细胞疗法(adoptive cell therapy,ACT),它们通过基因修饰技术赋予天然T细胞特异性识别肿瘤的受体来治疗癌症。CAR-T疗法针对复发或难治性血液系统恶性肿瘤,尤其是在急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的治疗中展现出令人瞩目的临床效果,但对实体瘤的治疗效果却不尽如人意。靶向肿瘤抗原的TCR-T疗法已在临床上证明可以有效治疗实体瘤,并取得了令人鼓舞的临床数据。但是,TCR-T疗法也面临一些挑战,例如靶向肿瘤抗原的选择、肿瘤特异性TCR的选择和优化、TCR-T的体内持久性和临床安全性等。综述TCR-T疗法的临床发展现状和其非临床研究动物模型的应用,并讨论了动物模型在克服当前限制性因素中的应用,以期待TCR-T疗法使更多肿瘤患者受益。Abstract: T cell receptor-engineered T cells (TCR-T) and chimeric antigen receptor T cells (CAR-T) therapies are two main types of adoptive cell therapy(ACT), which can treat cancer by giving natural T cells specific recognition of tumor receptors through gene modification technique. CAR-T therapy has achieved remarkable success in relapsed or refractory hematological malignancies, especially in the treatment of acute lymphoblastic leukemia (ALL), yet with less effect on solid tumors. TCR-T therapy has displayed some advantage over CAR-T therapy in treating solid tumors with inspiring clinical data. However, TCR-T therapy is faced with some challenges, including the selection of tumor-specific/associated antigens, selection and optimization of tumor-specific TCR, the persistence of TCR-T, and the safety of TCR-T therapy. This paper reviews the current development of TCR-T therapy and application of its preclinical animal models,and also discusses the progress made in the research on preclinical animal models employed to overcome the restrictive factors of TCR-T therapy, in the hope that TCR-T therapy will eventually benefit more cancer patients in the future.
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Keywords:
- TCR-T cell therapy /
- preclinical animal model /
- solid tumor
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