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01-11-2018 | Clinical Trial Report

Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial

Authors: Yu Yao, Feifei Luo, Chao Tang, Dikang Chen, Zhiyong Qin, Wei Hua, Ming Xu, Ping Zhong, Shuangquan Yu, Di Chen, Xiaojie Ding, Yi Zhang, Xiujuan Zheng, Jiao Yang, Jiawen Qian, Yuting Deng, Dave S. B. Hoon, Jian Hu, Yiwei Chu, Liangfu Zhou

Published in: Cancer Immunology, Immunotherapy | Issue 11/2018

Abstract

Dendritic cell (DC)-based vaccination is a promising approach for active-specific immunotherapy, but is currently of limited efficacy. The safety and effectiveness of a DC vaccine (DCV) loaded with glioblastoma stem cell-like (GSC) antigens was assessed in glioblastoma multiforme (GBM) patients. In this double-blind, placebo-controlled phase II clinical trial, 43 GBM patients were randomized after surgery at a 1:1 ratio to receive either DCV (n = 22) or normal saline placebo (n = 21). Overall survival (OS) and progression-free survival (PFS) were analysed. Participants were stratified into different molecular subgroups based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT). Plasma cytokine levels, tumor-infiltrating lymphocyte numbers and immune co-inhibitory molecules PD-L1 and B7-H4 were also assessed. Multivariate Cox regression analysis revealed that DCV treatment significantly prolonged OS (p = 0.02) after adjusting for IDH1 and TERT promoter MT and B7-H4 expression, primary vs recurrent GBM. Among IDH1^{wild type (WT)} TERT^MT patients, DCV treatment significantly prolonged OS (p < 0.01) and PFS (p = 0.03) and increased plasma levels of cytokines CCL22 and IFN-γ compared with placebo. Patients with low B7-H4 expression showed significantly prolonged OS (p = 0.02) after DCV treatment. Therefore, IDH1^WTTERT^MT and low B7-H4 expression identified subgroups of GBM patients more responsive to GSC DCV-based specific active-immunotherapy.

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Title: Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial
Authors: Yu Yao
Feifei Luo
Chao Tang
Dikang Chen
Zhiyong Qin
Wei Hua
Ming Xu
Ping Zhong
Shuangquan Yu
Di Chen
Xiaojie Ding
Yi Zhang
Xiujuan Zheng
Jiao Yang
Jiawen Qian
Yuting Deng
Dave S. B. Hoon
Jian Hu
Yiwei Chu
Liangfu Zhou
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 11/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2232-y

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