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  • Open Access

The generation and analysis of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P452

https://doi.org/10.1186/2051-1426-3-S2-P452

  • Published:

Keywords

  • Recombinant Adenovirus
  • Human Dendritic Cell
  • Vector Gene Delivery
  • Late Gene Expression
  • Metastatic Colorectal Cancer Patient

We have reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]), in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. CEA, MUC1, and brachyury are tumor-associated antigens (TAA) expressed on a wide range of human tumors. Ad5 [E1-, E2b-]–CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. The Ad5 [E1-, E2b-]–CEA vector encodes the entire CEA sequence modified to express an enhancer T-cell epitope. We report here the development of novel Ad5 [E1-, E2b-]–brachyury and Ad5 [E1-, E2b-]–MUC-1 vaccine constructs. The Ad5 [E1-, E2b-]–brachyury vector was constructed to encode the entire brachyury gene devoid of 25 amino acids involved in DNA binding, and modified to express an enhancer T cell epitope. The Ad5 [E1-, E2b-]–MUC-1 vector was constructed to encode the entire MUC-1 transgene with eight agonist epitopes, including five in the C-terminus. Our results show that these constructs (CEA, MUC1 and brachyury) are capable of activation, as well as generation of antigen specific T cells in vitro, and of inducing antigen-specific T cells in vaccinated mice. We have also demonstrated that the use of a combination of the three vaccines (designated Tri-Ad5) displays little, if any, antigenic competition in in vitro studies of human dendritic cells for antigen-specific T cell activation and generation, or in murine vaccination studies. The studies reported here support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.

Authors’ Affiliations

(1)
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
(2)
Etubics Corporation, Seattle, WA, USA
(3)
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
(4)
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Copyright

© Tsang et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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