Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
J Exp Med. 2012 Feb 13;209(2):201-9. doi: 10.1084/jem.20112275.
Since it became clear that all cancer cells express tumor-specific and tumor-selective antigens generated by genetic alterations and epigenetic dysregulation, the immunology community has embraced the possibility of designing therapies to induce targeted antitumor immune responses. The potential therapeutic specificity and efficacy of such treatments are obvious to anyone who studies the exquisite specificity and cytocidal potency of immune responses. However, the value assigned to a therapeutic modality by the oncology community at large does not depend on scientific principle; all that matters is how patients respond. The bar for the ultimate acceptance of a therapy requires more than anecdotal clinical responses; rather, the major modalities of cancer therapeutics, including surgery, chemotherapy, radiation therapy, and, more recently, drugs targeting oncogenes, have earned their place only after producing dramatic frequent clinical responses or demonstrating statistically significant survival benefits in large randomized phase 3 clinical trials, leading to FDA approval. Although tumor-targeted antibodies have certainly cleared this bar, immunotherapies aimed at harnessing antitumor cellular responses have not-until now.
自从人们清楚地认识到所有癌细胞都表达由遗传改变和表观遗传失调产生的肿瘤特异性和肿瘤选择性抗原以来，免疫学领域已经接受了设计疗法以诱导靶向抗肿瘤免疫反应的可能性。任何研究过免疫反应的精细特异性和细胞杀伤效力的人都清楚地看到了此类治疗的潜在治疗特异性和疗效。然而，肿瘤学领域赋予一种治疗方式的价值并不取决于科学原理；重要的是患者的反应如何。一种疗法最终被接受的标准不仅仅是偶然的临床反应；相反，癌症治疗的主要方式，包括手术、化疗、放疗，以及最近针对致癌基因的药物，只有在产生显著频繁的临床反应或在大型随机 3 期临床试验中显示出统计学上显著的生存获益后，才获得了 FDA 的批准。尽管肿瘤靶向抗体肯定已经达到了这一标准，但旨在利用抗肿瘤细胞反应的免疫疗法直到现在还没有。
