A phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma
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Published:2022-10-28
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Tan Tira J., Ang W. X. GladysORCID, Wang Who-Whong, Chong Hui-Shan, Tan Sze HueyORCID, Cheong Rachael, Chia John Whay-Kuang, Syn Nicholas L., Shuen Wai HoORCID, Ba Rebecca, Kaliaperumal Nivashini, Au Bijin, Hopkins Richard, Li Xinhua, Tan Aaron C.ORCID, Seet Amanda O. L., Connolly John E., Arkachaisri ThaschaweeORCID, Chew ValerieORCID, Lajam Ahmad bin Mohamed, Guo Dianyan, Chew Marvin Z. W., Wasser MartinORCID, Kumar Pavanish, Albani SalvatoreORCID, Toh Han ChongORCID
Abstract
AbstractCancer vaccines as immunotherapy for solid tumours are currently in development with promising results. We report a phase 1 study of Ad-sig-hMUC1/ecdCD40L (NCT02140996), an adenoviral-vector vaccine encoding the tumour-associated antigen MUC1 linked to CD40 ligand, in patients with advanced adenocarcinoma. The primary objective of this study is safety and tolerability. We also study the immunome in vaccinated patients as a secondary outcome. This trial, while not designed to determine clinical efficacy, reports an exploratory endpoint of overall response rate. The study meets its pre-specified primary endpoint demonstrating safety and tolerability in a cohort of 21 patients with advanced adenocarcinomas (breast, lung and ovary). The maximal dose of the vaccine is 1 ×1011viral particles, with no dose limiting toxicities. All drug related adverse events are of low grades, most commonly injection site reactions in 15 (71%) patients. Using exploratory high-dimensional analyses, we find both quantitative and relational changes in the cancer immunome after vaccination. Our data highlights the utility of high-dimensional analyses in understanding and predicting effective immunotherapy, underscoring the importance of immune competency in cancer prognosis.
Funder
National Medical Research Council Singapore
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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