Tracking Neoantigens by Personalized Circulating Tumor DNA Sequencing during Checkpoint Blockade Immunotherapy in Non‐Small Cell Lung Cancer

• DOI: 10.1002/advs.201903410
• Publication Date: 2020-03-27T05:05:46Z
• Authors: Qingzhu Jia; Luting Chiu; Shuangxiu Wu; Jian Bai; Lina Peng; Linpeng Zheng; Rui Zang; Xueqin Li; Bibo Yuan; Yixing Gao; Dingyong Wu; Xiaohong Li; Lin Wu; Jianguo Sun; Ji He; Bruce W. S. Robinson; Bo Zhu
• Keywords: Immune checkpoint; Exome; Cancer Immunotherapy; Personalized Medicine

Abstract The evolutionary dynamics of tumor‐associated neoantigens carry information about drug sensitivity and resistance to the immune checkpoint blockade (ICB). However, spectrum somatic mutations is highly heterogeneous among patients, making it difficult track by circulating tumor DNA (ctDNA) sequencing using “one size fits all” commercial gene panels. Thus, individually customized panels (ICPs) are needed neoantigen evolution comprehensively during ICB treatment. Dominant predicted from whole exome data for treatment‐naïve tissues. Panels targeting used personalized ctDNA sequencing. Analyzing ten patients with non‐small cell lung cancer, ICPs effective tracking most dominant (80–100%) in serial peripheral blood samples, detect substantially more genes (18–30) than capacity current A 50% decrease concentration after eight weeks administration associated favorable progression‐free survival. Furthermore, at individual level, magnitude early response correlated subsequent change burden. application ICP‐based expected improve understanding ICB‐driven provide management strategies that optimize clinical benefits immunotherapies.