Jäger Elke, Jäger Dirk, Knuth Alexander
II. Medizinische Klinik, Hämatologie-Onkologie, Frankfurt, Germany.
Int J Cancer. 2003 Oct 10;106(6):817-20. doi: 10.1002/ijc.11292.
The specific activation of the immune system to control cancer growth in vivo has been a long-standing goal in cancer immunology and medical oncology. The identification of tumor-associated antigens has provided the basis for new concepts in antigen-specific immunotherapy. The first clinical trials on cancer vaccines were designed to evaluate the toxicity and objectively measurable immunologic effects in relation to clinical developments mostly in patients with metastatic disease. MHC class I- and II-restricted peptide epitopes, antigenic proteins, viral constructs, mini-genes and whole tumor cells have been used either alone or combined with different cytokines (i.e., IL-2, IL-12, GM-CSF), adjuvants (incomplete Freund's adjuvant, montanide, QS21) or with dendritic cells to induce specific immune responses in vivo. Standardized assay systems to evaluate the immunologic effects of cancer vaccines have been established. Clinical developments during and after vaccination were followed in relation to vaccine-induced immune responses. Prognostic tumor features, i.e., homogeneity of tumor antigen and MHC class I/II expression and intratumoral cellular infiltrates, have been identified that may help to select patients who are more likely to benefit from antigen-specific cancer vaccines in the future.
在体内特异性激活免疫系统以控制癌症生长一直是癌症免疫学和医学肿瘤学中长期追求的目标。肿瘤相关抗原的鉴定为抗原特异性免疫治疗的新概念提供了基础。首批癌症疫苗临床试验旨在评估毒性以及与临床进展相关的客观可测量的免疫效应,主要针对转移性疾病患者。MHC I类和II类限制性肽表位、抗原蛋白、病毒构建体、微型基因和完整肿瘤细胞已单独使用或与不同细胞因子(如IL-2、IL-12、GM-CSF)、佐剂(不完全弗氏佐剂、蒙旦蜡、QS21)或与树突状细胞联合使用,以在体内诱导特异性免疫反应。已建立了评估癌症疫苗免疫效应的标准化检测系统。根据疫苗诱导的免疫反应对疫苗接种期间及之后的临床进展进行跟踪。已确定了预后肿瘤特征,即肿瘤抗原的同质性、MHC I类/II类表达以及肿瘤内细胞浸润,这些特征可能有助于选择未来更有可能从抗原特异性癌症疫苗中获益的患者。