CAR-T细胞治疗实体肿瘤:且行且思考
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摘要
由于T细胞免疫具有长效性、可放大性、多靶点性等特点,以T细胞为核心的肿瘤免疫治疗被认为是除手术外最有可能带来肿瘤治愈的治疗手段。尤其近年来不断累积的临床数据证实了以嵌合抗原受体修饰T(chimeric antigen receptor modified T, CAR-T)细胞为代表的细胞治疗的安全性与有效性,其中以CD19为靶点的CAR-T细胞疗法由于效果显著,已成为多数临床研究机构开展基因修饰T细胞治疗研究的模式疗法。但是,实践和理论均显示,CAR-T细胞在实体肿瘤的治疗中面临着更严峻的挑战,如何更加合理有效的开展CAR-T细胞治疗实体肿瘤仍需要不断地探索。本文回顾了CAR-T细胞治疗临床实践历程、治疗实体瘤的现状,阐述了需要解决的问题及未来的发展方向,旨在为CAR-T细胞治疗实体肿瘤提供借鉴及研究思路。
Due to the long-lasting, scalable, multi-targeting characteristics of T-cell immunity, T-cell-based tumor immunotherapy is considered to be the most likely means of bringing about tumor healing in addition to surgery. Especially in recent years, accumulating clinical data have confirmed the safety and effectiveness of cell therapy represented by chimeric antigen receptor modified T(CAR-T) cell. Among these, CAR-T therapy targeting CD19 has become a model therapy for genetic modified T cell therapy research in most institutions because of its remarkable effects. However, both practice and theory have suggested that CAR-T therapy faces more complicated problems in the treatment of solid tumors. How to use CAR-T cells to treat solid tumors reasonably and effectively still requires constant exploration and understanding. Here, we briefly summarize the current status of clinical practice of CAR-T cell therapy and its treatment of solid tumors, propose problems that need to be solved, and discuss the future research directions, in order to provide reference and research ideas for the treatment of solid tumors by CAR-T cells.
Due to the long-lasting, scalable, multi-targeting characteristics of T-cell immunity, T-cell-based tumor immunotherapy is considered to be the most likely means of bringing about tumor healing in addition to surgery. Especially in recent years, accumulating clinical data have confirmed the safety and effectiveness of cell therapy represented by chimeric antigen receptor modified T(CAR-T) cell. Among these, CAR-T therapy targeting CD19 has become a model therapy for genetic modified T cell therapy research in most institutions because of its remarkable effects. However, both practice and theory have suggested that CAR-T therapy faces more complicated problems in the treatment of solid tumors. How to use CAR-T cells to treat solid tumors reasonably and effectively still requires constant exploration and understanding. Here, we briefly summarize the current status of clinical practice of CAR-T cell therapy and its treatment of solid tumors, propose problems that need to be solved, and discuss the future research directions, in order to provide reference and research ideas for the treatment of solid tumors by CAR-T cells.
引文
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[24]陈晓彤,刘宝瑞.T细胞受体工程化T细胞抗肿瘤治疗的现状与挑战[J].中国肿瘤生物治疗杂志,2018,25(8):755-761.DOI:10.3872/j.issn.1007-385X.2018.08.001.
[25]NEWICK K,O'BRIEN S,MOON E,et al.CAR-T cell therapy for solid tumors[J].Annu Rev Med,2017,68(2):139-152.DOI:10.1146/annurev-med-062315-120245.
[26]刘宝瑞.实体肿瘤免疫治疗的关键问题与对策[J].中国肿瘤生物治疗杂志,2017,24(6):575-580.DOI:10.3872/j.issn.1007-385X.2017.06.001.
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[28]POZNANSKY M C,OLSZAK I T,FOXALL R,et al.Active movement of T cells away from a chemokine[J].Nat Med,2000,6(5):543-548.DOI:10.1038/75022.
[29]ABIKO K,MATSUMURA N,HAMANISHI J,et al.IFN-γfrom lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer[J].Br J Cancer,2015,112(9):1501-1509.DOI:10.1038/bjc.2015.101.
[30]JARNICKI AG,LYSAGHT J,TODRYK S,et al.Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor:influence of tumor environment on the induction of CD4+and CD8+regulatory T cells[J].J Immunol,2006,177(2):896-904.DOI:10.4049/jimmunol.177.2.896.
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