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

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

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish
Article number1903410
JournalAdvanced Science
Volume7
Issue number9
DOIs
Publication statusPublished - 1 May 2020

Fingerprint Dive into the research topics of 'Tracking Neoantigens by Personalized Circulating Tumor DNA Sequencing during Checkpoint Blockade Immunotherapy in Non-Small Cell Lung Cancer'. Together they form a unique fingerprint.

  • Cite this

    Jia, Q., Chiu, L., Wu, S., Bai, J., Peng, L., Zheng, L., Zang, R., Li, X., Yuan, B., Gao, Y., Wu, D., Li, X., Wu, L., Sun, J., He, J., Robinson, B. W. S., & Zhu, B. (2020). Tracking Neoantigens by Personalized Circulating Tumor DNA Sequencing during Checkpoint Blockade Immunotherapy in Non-Small Cell Lung Cancer. Advanced Science, 7(9), [1903410]. https://doi.org/10.1002/advs.201903410