The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research.
The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research.
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癌症抗原的优先次序：国家癌症研究所加速研究的试点项目。
DOI：
10.1158/1078-0432.ccr-09-0737
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发表时间：
2009-09-01
期刊：
影响因子：
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通讯作者：
Matrisian LM
中科院分区：
文献类型：
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作者：
Cheever MA;Allison JP;Ferris AS;Finn OJ;Hastings BM;Hecht TT;Mellman I;Prindiville SA;Viner JL;Weiner LM;Matrisian LM
美国国家癌症研究所（NCI）优先考虑癌症抗原的试点项目的目的是根据预先定义和预先加权的客观标准制定一个经过严格审查的癌症疫苗靶抗原优先列表。NCI的另一个目标是测试一种新的方法，根据层次分析法对翻译研究机会进行优先排序，以处理复杂的决策。抗原优先化涉及开发“理想”癌症抗原标准/特征的列表，使用成对比较将相对权重分配给那些标准，选择75种代表性抗原用于比较和排序，收集关于所选抗原的预定义标准的信息，并基于预定义的、预加权的标准对抗原排序。使用成对方法，按降序排列的标准加权结果为：（1）治疗功能，（2）免疫原性，（3）抗原在致癌性中的作用，（4）特异性，（5）抗原阳性细胞的表达水平和百分比，（6）干细胞表达，（7）抗原阳性癌症患者的数量，（8）抗原表位的数量和（9）抗原表达的细胞定位。75种抗原中没有一种具有“理想”癌抗原的所有特征。然而，46个在临床试验中具有免疫原性，其中20个在“治疗功能”类别中具有提示性临床疗效。这些发现反映了癌症疫苗领域的现状，强调了额外的有组织的努力和资金将加速治疗有效的癌症疫苗的开发的可能性，并强调了优先考虑的必要性。
The purpose of the National Cancer Institute (NCI) pilot project to prioritize cancer antigens was to develop a well-vetted ranked prioritized list of cancer vaccine target antigens based on pre-defined and pre-weighted objective criteria. An additional aim was for the NCI 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 pair-wise comparisons, selecting 75 representative antigens for comparison and ranking, assembling information on the pre-defined criteria for the selected antigens, and ranking the antigens based on the pre-defined, pre-weighted criteria. Using the pair-wise approach, the result of criteria weighting, in descending order was: (1) Therapeutic function, (2) Immunogenicity, (3) Role of the antigen in oncogenicity, (4) Specificity, (5) Expression level and percent of antigen positive cells, (6) Stem cell expression, (7) Number of patients with antigen positive cancers, (8) Number of antigenic epitopes and (9) 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.