Morris Emma, Hart Dan, Gao Liquan, Tsallios Aristotle, Xue Shao-An, Stauss Hans
Department of Immunology, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Blood Rev. 2006 Mar;20(2):61-9. doi: 10.1016/j.blre.2005.05.001. Epub 2005 Jun 22.
Antigen-specific tumor immunotherapy remains an attractive strategy for the treatment of malignancies. In this review we will discuss why, despite the identification of large numbers of T cell recognised tumor antigens, effective immunotherapy remains a formidable challenge. Effective strategies are needed to deal with the tolerogenic properties of many tumor antigens, and with the immunocompromised status of patients. We discuss different methods of generating tumor-specific T cells which are currently being evaluated in clinical practice, such as vaccination and adoptive transfer of tumor antigen-specific T cells. Finally, we shall discuss novel strategies in development, such as the adoptive transfer of T cell receptor (TCR) gene modified T cells to establish antigen-specific immunity in patients with leukemia and solid cancers. The transfer of validated high avidity TCRs, isolated from 'non-tolerant' repertoires or produced by in vitro affinity maturation, can serve to equip patient T cells with new anti-tumor specificities that are not naturally present in the autologous repertoire. TCR transfer into CD4(+) and CD8(+) T cells can serve to harness the function of both helper and cytotoxic T cells for tumor elimination and establishment of long-term tumor immunity.
抗原特异性肿瘤免疫疗法仍然是治疗恶性肿瘤的一种有吸引力的策略。在这篇综述中，我们将讨论为什么尽管已经鉴定出大量T细胞识别的肿瘤抗原，但有效的免疫疗法仍然是一项艰巨的挑战。需要有效的策略来应对许多肿瘤抗原的致耐受性特性以及患者的免疫受损状态。我们讨论了目前正在临床实践中评估的产生肿瘤特异性T细胞的不同方法，例如疫苗接种和肿瘤抗原特异性T细胞的过继转移。最后，我们将讨论正在开发的新策略，例如过继转移T细胞受体（TCR）基因修饰的T细胞，以在白血病和实体癌患者中建立抗原特异性免疫。从“非耐受性”库中分离或通过体外亲和力成熟产生的经过验证的高亲和力TCR的转移，可以使患者T细胞具备自体库中天然不存在的新的抗肿瘤特异性。将TCR转移到CD4(+)和CD8(+) T细胞中，可以利用辅助性T细胞和细胞毒性T细胞的功能来消除肿瘤并建立长期的肿瘤免疫。
