使用基因工程设计T细胞的过继性癌症免疫疗法:迈向临床的第一步。

Adoptive cancer immunotherapy using genetically engineered designer T-cells: First steps into the clinic.

作者信息

Eshhar Zelig

机构信息

The Weizmann Institute of Science, Department of Immunology, Rehovot, Israel.

出版信息

Curr Opin Mol Ther. 2010 Feb;12(1):55-63.

DOI:
Abstract

The treatment of patients with cancer using passive vaccination with antibodies has been demonstrated to be a promising option, particularly for 'soft tumors', most likely because of their greater accessibility compared with bulky solid tumors. While effector T-cells are efficient in the rejection of large organs and foreign tissues, the wide application of tumor-specific T-cells for cancer therapy has been limited by the inherent restriction of T-cell recognition to self antigens, and the difficulty in obtaining sufficient numbers of such cells with defined specificity. Advances in gene transfer and cell therapy have enabled the genetic modification of T-cells by the ectopic expression of predefined, specific receptor genes that redirect such 'designer cells' to any target of interest. This review discusses two approaches to applying redirected T-cells for adoptive cancer immunotherapy: the 'T-body' approach, which employs chimeric receptors with tumor-specific antibody-derived specificity, and the use of transgenes encoding tumor-specific T-cell receptors. Particular emphasis is placed on recent attempts using these approaches in the treatment of patients with cancer.

摘要

事实证明,使用抗体进行被动疫苗接种治疗癌症患者是一种很有前景的选择,特别是对于“软肿瘤”,这很可能是因为与体积较大的实体瘤相比,它们更容易被触及。虽然效应T细胞在排斥大器官和外来组织方面很有效,但肿瘤特异性T细胞在癌症治疗中的广泛应用受到T细胞对自身抗原识别的固有限制,以及难以获得足够数量具有明确特异性的此类细胞的限制。基因转移和细胞治疗的进展使得通过异位表达预定义的特异性受体基因对T细胞进行基因改造成为可能,这些基因可将此类“设计细胞”重定向到任何感兴趣的靶标。本文综述了将重定向T细胞应用于过继性癌症免疫治疗的两种方法:“T体”方法,即采用具有肿瘤特异性抗体衍生特异性的嵌合受体,以及使用编码肿瘤特异性T细胞受体的转基因。特别强调了最近使用这些方法治疗癌症患者的尝试。

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