Palucka Anna Karolina, Ueno Hideki, Fay Joseph, Banchereau Jacques
Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204, USA.
J Immunother. 2008 Nov-Dec;31(9):793-805. doi: 10.1097/CJI.0b013e31818403bc.
Cancer immunotherapy seeks to mobilize a patient's immune system for therapeutic benefit. It can be passive, that is, transfer of immune effector cells (T cells) or proteins (antibodies), or active, that is, vaccination. Early clinical trials testing vaccination with ex vivo generated dendritic cells (DCs) pulsed with tumor antigens provide a proof-of-principle that therapeutic immunity can be elicited. Yet, the clinical benefit measured by regression of established tumors in patients with stage IV cancer has been observed in a fraction of patients only. The next generation of DC vaccines is expected to generate large numbers of high avidity effector CD8 T cells and to overcome regulatory T cells and suppressive environment established by tumors, a major obstacle in metastatic disease. Therapeutic vaccination protocols will combine improved DC vaccines with chemotherapy to exploit immunogenic chemotherapy regimens. We foresee adjuvant vaccination in patients with resected tumors but at high risk of relapse to be based on in vivo targeting of DCs with fusion proteins containing anti-DCs antibodies, antigens from tumor stem/propagating cells, and DC activators.
癌症免疫疗法旨在调动患者的免疫系统以获得治疗益处。它可以是被动的，即转移免疫效应细胞（T细胞）或蛋白质（抗体），也可以是主动的，即接种疫苗。早期临床试验对用肿瘤抗原脉冲处理的体外生成的树突状细胞（DC）进行疫苗接种，提供了一种原理证明，即可以引发治疗性免疫。然而，在IV期癌症患者中，通过已建立肿瘤的消退来衡量的临床益处仅在一小部分患者中观察到。下一代DC疫苗有望产生大量高亲和力效应CD8 T细胞，并克服肿瘤建立的调节性T细胞和抑制性环境，这是转移性疾病中的一个主要障碍。治疗性疫苗接种方案将把改进的DC疫苗与化疗相结合，以利用免疫原性化疗方案。我们预见，对于已切除肿瘤但复发风险高的患者，辅助疫苗接种将基于用含有抗DC抗体、肿瘤干细胞/增殖细胞抗原和DC激活剂的融合蛋白对DC进行体内靶向。
