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基因修饰 T 细胞可提高过继性肿瘤免疫治疗的效果。

Genetic modification of T cells improves the effectiveness of adoptive tumor immunotherapy.

机构信息

Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Banacha 1A, Building F, 02-097 Warsaw, Poland.

出版信息

Arch Immunol Ther Exp (Warsz). 2010 Oct;58(5):347-54. doi: 10.1007/s00005-010-0091-0. Epub 2010 Aug 6.


DOI:10.1007/s00005-010-0091-0
PMID:20694520
Abstract

Appropriate combinations of immunotherapy and gene therapy promise to be more effective in the treatment of cancer patients than either of these therapeutic approaches alone. One such treatment is based on the application of patients' cytotoxic T cells, which can be activated, expanded, and genetically engineered to recognize particular tumor-associated antigens (TAAs). Because T cells recognizing TAAs might become unresponsive in the process of tumor development as a result of tumor evasion strategies, immunogenic viral antigens or alloantigens could be used for the expansion of cytotoxic T cells and then redirected through genetic engineering. This therapeutic approach has already demonstrated promising results in melanoma patients and could be used in the treatment of many other tumors. The graft-versus-leukemia, or more generally graft-versus-tumor, reaction based on the application of a donor lymphocyte infusion can also be ameliorated through the incorporation of suicide genes into donor lymphocytes. Such lymphocytes could be safely and more extensively used in tumor patients because they could be eliminated should a severe graft-versus-host reaction develop.

摘要

适当的免疫疗法和基因疗法的组合有望比单独使用这些治疗方法更有效地治疗癌症患者。其中一种治疗方法基于应用患者的细胞毒性 T 细胞,这些细胞可以被激活、扩增和基因工程改造,以识别特定的肿瘤相关抗原 (TAA)。由于 T 细胞识别 TAA 可能会由于肿瘤逃避策略而在肿瘤发展过程中变得无反应,因此免疫原性病毒抗原或同种抗原可用于细胞毒性 T 细胞的扩增,然后通过基因工程进行重定向。这种治疗方法已经在黑色素瘤患者中显示出有希望的结果,并且可以用于治疗许多其他肿瘤。基于供体淋巴细胞输注的移植物抗白血病,或更一般地移植物抗肿瘤反应,也可以通过将自杀基因纳入供体淋巴细胞来改善。由于这些淋巴细胞如果发生严重的移植物抗宿主反应,可以被安全地更广泛地用于肿瘤患者,因为可以将其消除。

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