Waldmann Thomas A
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1374, USA.
Annu Rev Med. 2006;57:65-81. doi: 10.1146/annurev.med.56.082103.104549.
MAbs directed toward tumor cells, tumor neovasculature, and host negative immunoregulatory elements (checkpoints) have emerged as useful immunotherapeutic agents against cancer. However, effective active modulation of the immune response with anticancer vaccines will require identifying appropriate tumor-rejection antigens; optimizing the interactions of peptides, antigen-presenting cells, and T cells; and blockading negative immunological checkpoints that impede an effective immune response. Checkpoints being targeted include CTLA-4 and PD1 that are negative signaling receptors expressed on activated T cells, CD4+CD25+ Foxp3-expressing Tregs (suppressor T cells), IL-2-mediated activation-induced cell death (AICD), and the cytokine TGFbeta.
针对肿瘤细胞、肿瘤新生血管以及宿主负性免疫调节元件（检查点）的单克隆抗体已成为对抗癌症的有效免疫治疗药物。然而，使用抗癌疫苗有效主动调节免疫反应将需要识别合适的肿瘤排斥抗原；优化肽、抗原呈递细胞和T细胞之间的相互作用；以及阻断阻碍有效免疫反应的负性免疫检查点。正在被靶向的检查点包括CTLA-4和PD1，它们是活化T细胞上表达的负性信号受体、表达CD4+CD25+ Foxp3的调节性T细胞（抑制性T细胞）、IL-2介导的活化诱导细胞死亡（AICD）以及细胞因子转化生长因子β。
