Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer
作者机构：State Key Laboratory of Biotherapy and Cancer CenterWest China HospltalSIchuan Universityand Collaborative Innovation Center tor BlotherapyChengdu 610041China Department of BiotherapyCancer CenterWest China HospitalSichuan UniversityChengduChina Department of OncologyCancer CenterShanghai Tenth People's HospitalTongil UniversityShanghai 200072China Department of RadiologyWest China Hospitalsichuan UniversityChengduSichuanChina YuceBio Technology CoLtdShenzhenChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第2期
页 面：519-530页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
基 金：We gratefully acknowledge all patients who participated and their families,as well as the investigators and staff at this cdinical study for their valuable contribution to this study.This study was supported by the National key research and development program of China(Grant number 2016YFC1303502) the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University.
主 题：vaccine doses specificity
摘 要：Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity.Dendritic cell(DCs)vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality.Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world.Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years,their efficacy is still unsatisfactory overall.Therefore,there is an urgent unmet clinical need for lung cancer treatment.Here,we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm,2 medical centers,pilot study initiated by the investigator(ChiCTR-ONC 16009100,NCT02956551).The patients enrolled were patients with heavily treated metastatic lung cancer.Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis.A total of 12 patients were enrolled in this study.A total of 85 vaccine treatments were administered with a median value of 5 doses/person(range:3-14 doses/person).In total,12-30 peptide-based neoantigens were selected for each patient.AIl treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects.The objective effectiveness rate was 25%;the disease control rate was 75%;the median progression-free survival was 5.5 months and the median overall survival was 7.9 months.This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.
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