Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Immunotherapy. 2009 Jul;1(4):679-90. doi: 10.2217/imt.09.20.
T-cell-based immunotherapy can be induced by nonspecific activation, by antigen-specific immunization, or by adoptive immunotherapy. In this review, progress in these areas is discussed as based on data from clinical trials for the treatment of metastatic melanoma. Nonspecific immunotherapy has been shown to result in low, but in some cases significant, levels of objective tumor responses, and is often associated with autoimmune reactions. Antigen-specific targeting of tumors via vaccination has only resulted in low to very low levels of objective responses, and these strategies seem to have most value when the T-cell repertoire is not affected by tolerance. Finally, adoptive immunotherapy can be applied by in vitro expansion of autologous lymphocytes that have escaped tolerance or by genetic transfer of allogeneic T-cell receptors (TCRs). Autologous adoptive T-cell transfer has resulted in a very high frequency of clinical responses when combined with chemotherapy and IL-2 administration in single-center studies. Although TCR gene transfer has, until now, only resulted in a low frequency of clinical responses, it does have a broader application potential, and optimization of this strategy is likely to improve its efficacy.
T 细胞为基础的免疫疗法可通过非特异性激活、抗原特异性免疫或过继免疫疗法来诱导。在本综述中，根据转移性黑色素瘤治疗的临床试验数据，讨论了这些领域的进展。非特异性免疫疗法已显示出低但在某些情况下具有显著的客观肿瘤反应水平，并常伴有自身免疫反应。通过疫苗接种对肿瘤进行抗原特异性靶向治疗仅导致低至非常低水平的客观反应，并且当 T 细胞库不受耐受影响时，这些策略似乎最有价值。最后，过继免疫疗法可以通过体外扩增逃避耐受的自体淋巴细胞或通过同种异体 T 细胞受体 (TCR) 的基因转移来应用。在单中心研究中，自体过继 T 细胞转移与化疗和 IL-2 联合应用时，可导致非常高的临床反应频率。尽管 TCR 基因转移到目前为止仅导致低频率的临床反应，但它确实具有更广泛的应用潜力，并且优化这种策略可能会提高其疗效。
