Combined TCR Repertoire Profiles and Blood Cell Phenotypes Predict Melanoma Patient Response to Personalized Neoantigen Therapy plus Anti-PD-1

被引：42

作者：

Poran, Asaf ^{[1
]}

Scherer, Julian ^{[1
]}

Bushway, Meghan E. ^{[1
]}

Besada, Rana ^{[1
]}

Balogh, Kristen N. ^{[1
]}

Wanamaker, Amy ^{[1
]}

Williams, Reid G. ^{[1
]}

Prabhakara, Jasmina ^{[1
]}

Ott, Patrick A. ^{[2
,3
]}

Hu-Lieskovan, Siwen ^{[4
]}

Khondker, Zakaria S. ^{[1
]}

Gaynor, Richard B. ^{[1
]}

Rooney, Michael S. ^{[1
]}

Srinivasan, Lakshmi ^{[1
]}

机构：

[1] Neon Therapeut BioNTech US, Cambridge, MA 02139 USA

[2] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA

来源：

CELL REPORTS MEDICINE | 2020年 / 1卷 / 08期

关键词：

CANCER; DIVERSITY; REVEALS;

D O I：

10.1016/j.xcrm.2020.100141

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

T cells use highly diverse receptors (TCRs) to identify tumor cells presenting neoantigens arising from genetic mutations and establish anti-tumor activity. Immunotherapy harnessing neoantigen-specific T cells to target tumors has emerged as a promising clinical approach. To assess whether a comprehensive peripheral mononuclear blood cell analysis predicts responses to a personalized neoantigen cancer vaccine combined with anti-PD-1 therapy, we characterize the TCR repertoires and T and B cell frequencies in 21 patients with metastatic melanoma who received this regimen. TCR-alpha/beta-chain sequencing reveals that prolonged progression-free survival (PFS) is strongly associated with increased clonal baseline TCR repertoires and longitudinal repertoire stability. Furthermore, the frequencies of antigen-experienced T and B cells in the peripheral blood correlate with repertoire characteristics. Analysis of these baseline immune features enables prediction of PFS following treatment. This method offers a pragmatic clinical approach to assess patients' immune state and to direct therapeutic decision making.

引用

页数：14

共 44 条

[1] Building and Optimizing a Virus-specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections [J].