Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC

Bibliographic Details
Title: Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC
Authors: Caroline Tosch, Bérangère Bastien, Luc Barraud, Benoit Grellier, Virginie Nourtier, Murielle Gantzer, Jean Marc Limacher, Eric Quemeneur, Kaïdre Bendjama, Xavier Préville
Source: Journal for ImmunoTherapy of Cancer, Vol 5, Iss 1, Pp 1-10 (2017)
Publisher Information: BMJ Publishing Group, 2017.
Publication Year: 2017
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: Cancer vaccine, Viral vaccine, Tumor associated antigen, Lung cancer, T cell response, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Abstract Background Advanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine. Method The TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC. 78 patients from the TIME study carrying the HLA-A02*01 haplotype were analyzed using combinatorial encoding of MHC multimers to detect low frequencies of cellular immune responses to TG4010 and other unrelated TAA. Results We report that improvement of survival under TG4010 treatment correlated with development of T cell responses against MUC1. Interestingly, responses against MUC1 were associated with broadening of CD8 responses against non-targeted TAA, thus demonstrating induction of epitope spreading. Conclusion Our results support the causality of specific T-cell response in improved survival in NSCLC. Additionally, vaccine induced epitope spreading to other TAA participates to the enrichment of the diversity of the anti-tumor response. Hence, TG4010 appears as a useful therapeutic option to maximize response rate and clinical benefit in association with other targeted immuno-modulators. Trial registration Registered on ClinicalTrials.gov under identifier NCT01383148 on June 23rd, 2011.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2051-1426
Relation: http://link.springer.com/article/10.1186/s40425-017-0274-x; https://doaj.org/toc/2051-1426
DOI: 10.1186/s40425-017-0274-x
Access URL: https://doaj.org/article/76dc2c8570884a3c903109baf301346e
Accession Number: edsdoj.76dc2c8570884a3c903109baf301346e
Database: Directory of Open Access Journals
More Details
ISSN:20511426
DOI:10.1186/s40425-017-0274-x
Published in:Journal for ImmunoTherapy of Cancer
Language:English