Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers.
Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers.
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DOI：
10.1158/1078-0432.ccr-10-2234
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发表时间：
2011-05-15
期刊：
影响因子：
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通讯作者：
Disis ML
中科院分区：
文献类型：
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作者：
Butterfield LH;Palucka AK;Britten CM;Dhodapkar MV;Håkansson L;Janetzki S;Kawakami Y;Kleen TO;Lee PP;Maccalli C;Maecker HT;Maino VC;Maio M;Malyguine A;Masucci G;Pawelec G;Potter DM;Rivoltini L;Salazar LG;Schendel DJ;Slingluff CL Jr;Song W;Stroncek DF;Tahara H;Thurin M;Trinchieri G;van Der Burg SH;Whiteside TL;Wigginton JM;Marincola F;Khleif S;Fox BA;Disis ML
为了促进创新免疫治疗方法的发展，特别是对于利用个性化治疗潜在益处的治疗概念，需要开发和验证工具来识别可以从免疫治疗中受益的患者。尽管付出了巨大的努力，但我们还不知道要测量哪些抗肿瘤免疫参数，以及哪些检测方法最适合这些测量。iSBTc-SITC、FDA和NCI合作解决癌症免疫治疗的这些问题。在这里，我们回顾了主要的挑战，给出了方法和解决方案的例子，并提出了我们的建议。虽然特定的免疫参数和测定尚未得到验证，但我们建议遵循标准化（准确、精确和可重复）的方案，并使用功能测定法进行试验的主要免疫读数；考虑建立中央实验室，对大型多机构试验进行免疫监测；以及对任何细胞产物特异性的几种表型和功能潜在效力测定的标准化测试。当报告结果时，QA/QC执行完整，应包括真正具有代表性的原始数据和分析性能特征的选定示例。最后，为了促进对免疫的多个方面进行更广泛的分析，并收集有关变异的数据，我们建议除了细胞和血清外，还应将RNA和DNA样本（在标准化条件下）储存起来，以供以后检测。我们还建议抽取足够的血液，以便对试验中提出的主要假设进行有计划的测试，并储存额外的基线和治疗后血液，用于测试现场出现的新假设（或产生新假设）。
To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of anti-tumor immunity to measure and which assays are optimal for those measurements. The iSBTc-SITC, FDA and NCI partnered to address these issues for immunotherapy of cancer. Here, we review the major challenges, give examples of approaches and solutions and present our recommendations. While specific immune parameters and assays are not yet validated, we recommend following standardized (accurate, precise and reproducible) protocols and use of functional assays for the primary immunologic readouts of a trial; consideration of central laboratories for immune monitoring of large, multi-institutional trials; and standardized testing of several phenotypic and functional potential potency assays specific to any cellular product. When reporting results, the full QA/QC performed, selected examples of truly representative raw data and assay performance characteristics should be included. Lastly, to promote broader analysis of multiple aspects of immunity, and gather data on variability, we recommend that in addition to cells and serum, that RNA and DNA samples be banked (under standardized conditions) for later testing. We also recommend that sufficient blood be drawn to allow for planned testing of the primary hypothesis being addressed in the trial, and that additional baseline and post-treatment blood is banked for testing novel hypotheses (or generating new hypotheses) that arise in the field.