INSERM, U892, Nantes, F-44007, France.
Target Oncol. 2012 Mar;7(1):3-14. doi: 10.1007/s11523-012-0207-z. Epub 2012 Feb 15.
The adoptive transfer of tumor antigen-specific T cells recently achieved clinical efficacy for a fraction of melanoma patients refractory to other therapies. Unfortunately, the application of this strategy to the remaining melanoma and most other cancer patients is hampered by the difficulty to generate high-affinity tumor-reactive T cells. Two strategies are currently developed to extend the feasibility of this therapeutic approach: clinical grade tool production for MHC-peptide multimer-driven sorting of antigen-specific T cells from the endogenous peripheral T cell repertoire and de novo engineering of the missing repertoire by genetic transfer of cloned specific T cell receptor (TCR) into T cells. The expected multiplication of adoptive transfer treatments, by these strategies, and their careful evaluation should enable the cure of a number of otherwise compromised cancer patients and to gain insight into the characteristics of transferred T cells best fitted to eradicate tumor cells, in terms of antigen specificities, phenotype, and functions. In particular, identification of tumor-rejection antigens by this approach would improve the design and efficacy of all immunotherapeutic approaches.
肿瘤抗原特异性 T 细胞的过继转移最近在部分对其他治疗方法耐药的黑色素瘤患者中取得了临床疗效。不幸的是，由于难以产生高亲和力的肿瘤反应性 T 细胞，该策略在剩余的黑色素瘤和大多数其他癌症患者中的应用受到阻碍。目前正在开发两种策略来扩大这种治疗方法的可行性：临床级工具生产，用于 MHC-肽多聚体驱动的从内源性外周 T 细胞库中分拣抗原特异性 T 细胞，以及通过将克隆特异性 T 细胞受体（TCR）遗传转移到 T 细胞中从头设计缺失的库。通过这些策略，预计过继转移治疗的数量将增加，并且对其进行仔细评估将使许多其他有风险的癌症患者得到治愈，并深入了解最适合清除肿瘤细胞的转导 T 细胞的特征，包括抗原特异性、表型和功能。特别是，通过这种方法鉴定肿瘤排斥抗原将提高所有免疫治疗方法的设计和疗效。
