PT - JOURNAL ARTICLE AU - Caroline Tosch AU - Bérangère Bastien AU - Luc Barraud AU - Benoit Grellier AU - Virginie Nourtier AU - Murielle Gantzer AU - Jean Marc Limacher AU - Eric Quemeneur AU - Kaïdre Bendjama AU - Xavier Préville TI - Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC AID - 10.1186/s40425-017-0274-x DP - 2017 Dec 01 TA - Journal for ImmunoTherapy of Cancer PG - 70 VI - 5 IP - 1 4099 - http://jitc.bmj.com/content/5/1/70.short 4100 - http://jitc.bmj.com/content/5/1/70.full SO - J Immunother Cancer2017 Dec 01; 5 AB - 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.Abbreviations:CIConfidence intervalCMVCytomegalovirusCTChemotherapyHDHigh diversityHLAHuman leukocyte antigenHRHazard ratioLDLow diversityLODLimit of detectionMHCMajor histocompatibility complexMUC1Mucin 1MVAModified vaccinia virus AnkaraNSCLCNon small cell lung cancerPBMCPeripheral blood mononuclear cellTAATumor associated antigens