Cheever Martin A, Allison James P, Ferris Andrea S, Finn Olivera J, Hastings Benjamin M, Hecht Toby T, Mellman Ira, Prindiville Sheila A, Viner Jaye L, Weiner Louis M, Matrisian Lynn M
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Clin Cancer Res. 2009 Sep 1;15(17):5323-37. doi: 10.1158/1078-0432.CCR-09-0737.
The purpose of the National Cancer Institute pilot project to prioritize cancer antigens was to develop a well-vetted, priority-ranked list of cancer vaccine target antigens based on predefined and preweighted objective criteria. An additional aim was for the National Cancer Institute to test a new approach for prioritizing translational research opportunities based on an analytic hierarchy process for dealing with complex decisions. Antigen prioritization involved developing a list of "ideal" cancer antigen criteria/characteristics, assigning relative weights to those criteria using pairwise comparisons, selecting 75 representative antigens for comparison and ranking, assembling information on the predefined criteria for the selected antigens, and ranking the antigens based on the predefined, preweighted criteria. Using the pairwise approach, the result of criteria weighting, in descending order, was as follows: (a) therapeutic function, (b) immunogenicity, (c) role of the antigen in oncogenicity, (d) specificity, (e) expression level and percent of antigen-positive cells, (f) stem cell expression, (g) number of patients with antigen-positive cancers, (h) number of antigenic epitopes, and (i) cellular location of antigen expression. None of the 75 antigens had all of the characteristics of the ideal cancer antigen. However, 46 were immunogenic in clinical trials and 20 of them had suggestive clinical efficacy in the "therapeutic function" category. These findings reflect the current status of the cancer vaccine field, highlight the possibility that additional organized efforts and funding would accelerate the development of therapeutically effective cancer vaccines, and accentuate the need for prioritization.
美国国立癌症研究所（National Cancer Institute）对癌症抗原进行优先级排序的试点项目旨在，根据预先定义和预先加权的客观标准，制定一份经过充分审核、按优先级排序的癌症疫苗靶抗原清单。另一个目标是让美国国立癌症研究所测试一种基于层次分析法（analytic hierarchy process）来处理复杂决策的新方法，以对转化研究机会进行优先级排序。抗原优先级排序包括制定一份“理想”癌症抗原标准/特征清单，通过两两比较为这些标准赋予相对权重，选择75种代表性抗原进行比较和排序，收集所选抗原预先定义标准的相关信息，并根据预先定义和预先加权的标准对抗原进行排序。采用两两比较法，标准权重结果从高到低依次如下：（a）治疗功能，（b）免疫原性，（c）抗原在致癌性中的作用，（d）特异性，（e）表达水平和抗原阳性细胞百分比，（f）干细胞表达，（g）抗原阳性癌症患者数量，（h）抗原表位数量，以及（i）抗原表达的细胞定位。这75种抗原中没有一种具备理想癌症抗原的所有特征。然而，有46种在临床试验中具有免疫原性，其中20种在“治疗功能”类别中具有提示性的临床疗效。这些发现反映了癌症疫苗领域的现状，凸显了进一步有组织的努力和资金投入将加速治疗有效的癌症疫苗研发的可能性，并强调了进行优先级排序的必要性。
