Targeting cancer-specific mutations by T cell receptor gene therapy.
Targeting cancer-specific mutations by T cell receptor gene therapy.
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DOI：
10.1016/j.coi.2015.02.005
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发表时间：
2015-04
影响因子：
7
通讯作者：
Schreiber H
中科院分区：
文献类型：
--
作者：
Blankenstein T;Leisegang M;Uckert W;Schreiber H
癌症基因组测序、识别所有体细胞突变和将突变特异性T细胞受体(TCR)基因移植到T细胞进行过继转移的简单易行，首次实现了一种真正针对肿瘤的有效疗法。突变特异性TCR基因治疗可能以最小的毒性达到最佳疗效。最近的临床数据证实了来自实验癌症模型的长期证据，即由肿瘤特异性体细胞突变编码的抗原可能是过继T细胞治疗的最佳靶点。悬而未决的问题是，有多少体细胞突变产生合适的表位，是否只有个体特异的或重复出现的体细胞突变才符合合适的表位，以及如何最有效地获得新抗原特异性TCR。需要考虑肿瘤的异质性；因此，重要的是确定早期发生的免疫原性驱动突变，这些突变对癌细胞的生存至关重要，并且存在于所有癌细胞中。
The ease of sequencing the cancer genome, identifying all somatic mutations and grafting mutation-specific T cell receptor (TCR) genes into T cells for adoptive transfer allow, for the first time, a truly tumor-specific and effective therapy. Mutation-specific TCR gene therapy might achieve optimal efficacy with least possible toxicity. Recent clinical data confirm the long-standing evidence from experimental cancer models that antigens encoded by the tumor-specific somatic mutations are potentially the best targets for adoptive T cell therapy. Open questions are, how many somatic mutations create suitable epitopes, whether only individual-specific or also recurrent somatic mutations qualify as suitable epitopes and how neoantigen-specific TCRs are most efficiently obtained. Tumor heterogeneity needs to be considered; therefore, it will be important to identify immunogenic driver mutations that occurred early, are essential for cancer cell survival and present in all cancer cells.