Phase I Study of a Poxviral TRICOM-Based Vaccine Directed Against the Transcription Factor Brachyury

Clin Cancer Res. 2017 Nov 15;23(22):6833-6845. doi: 10.1158/1078-0432.CCR-17-1087. Epub 2017 Aug 30.


Purpose: The transcription factor brachyury has been shown in preclinical studies to be a driver of the epithelial-to-mesenchymal transition (EMT) and resistance to therapy of human tumor cells. This study describes the characterization of a Modified Vaccinia Ankara (MVA) vector-based vaccine expressing the transgenes for brachyury and three human costimulatory molecules (B7.1, ICAM-1, and LFA-3, designated TRICOM) and a phase I study with this vaccine.Experimental Design: Human dendritic cells (DC) were infected with MVA-brachyury-TRICOM to define their ability to activate brachyury-specific T cells. A dose-escalation phase I study (NCT02179515) was conducted in advanced cancer patients (n = 38) to define safety and to identify brachyury-specific T-cell responses.Results: MVA-brachyury-TRICOM-infected human DCs activated CD8+ and CD4+ T cells specific against the self-antigen brachyury in vitro No dose-limiting toxicities were observed due to vaccine in cancer patients at any of the three dose levels. One transient grade 3 adverse event (AE) possibly related to vaccine (diarrhea) resolved without intervention and did not recur with subsequent vaccine. All other AEs related to vaccine were transient and ≤grade 2. Brachyury-specific T-cell responses were observed at all dose levels and in most patients.Conclusions: The MVA-brachyury-TRICOM vaccine directed against a transcription factor known to mediate EMT can be administered safely in patients with advanced cancer and can activate brachyury-specific T cells in vitro and in patients. Further studies of this vaccine in combination therapies are warranted and planned. Clin Cancer Res; 23(22); 6833-45. ©2017 AACR.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-1 Antigen / genetics
  • Biomarkers, Tumor
  • CD58 Antigens / genetics
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Fetal Proteins / genetics
  • Fetal Proteins / immunology*
  • Genetic Vectors* / genetics
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Middle Aged
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / mortality
  • Neoplasms / therapy*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • T-Cell Antigen Receptor Specificity / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transgenes
  • Treatment Outcome
  • Vaccinia virus* / genetics


  • B7-1 Antigen
  • Biomarkers, Tumor
  • CD58 Antigens
  • Cancer Vaccines
  • Fetal Proteins
  • T-Box Domain Proteins
  • Intercellular Adhesion Molecule-1
  • Brachyury protein