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Molecular Cancer Therapeutics
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Large Molecule Therapeutics

Herpes Simplex Virus Glycoprotein D Targets a Specific Dendritic Cell Subset and Improves the Performance of Vaccines to Human Papillomavirus-Associated Tumors

Bruna F.M.M. Porchia, Ana Carolina R. Moreno, Rodrigo N. Ramos, Mariana O. Diniz, Laís Helena T.M. de Andrade, Daniela S. Rosa, José Alexandre M. Barbuto, Silvia B. Boscardin and Luís Carlos S. Ferreira
Bruna F.M.M. Porchia
1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Ana Carolina R. Moreno
1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Rodrigo N. Ramos
2Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Mariana O. Diniz
1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Laís Helena T.M. de Andrade
1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Daniela S. Rosa
3Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo-UNIFESP, São Paulo, Brazil.
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José Alexandre M. Barbuto
2Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Silvia B. Boscardin
4Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Luís Carlos S. Ferreira
1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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  • For correspondence: lcsf@usp.br
DOI: 10.1158/1535-7163.MCT-17-0071
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Abstract

Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7). Two subcutaneous doses of gDE7, admixed with poly (I:C), conferred complete and long-lasting therapeutic antitumor protection on mice previously challenged with tumor cells expressing the HPV-16 oncoproteins. The vaccine induced multifunctional E7-specific CD8+ T cells with cytotoxic activity and effector memory phenotype (CD44+ CD62Llow). In addition, gDE7 admixed with poly (I:C) vaccination controlled the expansion of tumor-induced regulatory T cells and myeloid-derived suppressor cells. More importantly, gDE7 activated mouse CD11c+ CD8α+ and human BDCA3+ dendritic cells (DC), specialized in antigen cross-presentation to CD8+ T cells, under in vitro conditions. These results indicated that the activation of a specific DC population, mediated by gD, improved the antigen-specific immune responses and the therapeutic performance induced by antitumor vaccines. These results open perspectives for the clinical testing of gDE7-based vaccines under the concept of active immunization as a tool for the therapeutic control of cancer. Mol Cancer Ther; 16(9); 1–12. ©2017 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Received January 22, 2017.
  • Revision received April 5, 2017.
  • Accepted May 9, 2017.
  • ©2017 American Association for Cancer Research.
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This OnlineFirst version was published on August 17, 2017
doi: 10.1158/1535-7163.MCT-17-0071

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Herpes Simplex Virus Glycoprotein D Targets a Specific Dendritic Cell Subset and Improves the Performance of Vaccines to Human Papillomavirus-Associated Tumors
Bruna F.M.M. Porchia, Ana Carolina R. Moreno, Rodrigo N. Ramos, Mariana O. Diniz, Laís Helena T.M. de Andrade, Daniela S. Rosa, José Alexandre M. Barbuto, Silvia B. Boscardin and Luís Carlos S. Ferreira
Mol Cancer Ther August 17 2017 DOI: 10.1158/1535-7163.MCT-17-0071

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Herpes Simplex Virus Glycoprotein D Targets a Specific Dendritic Cell Subset and Improves the Performance of Vaccines to Human Papillomavirus-Associated Tumors
Bruna F.M.M. Porchia, Ana Carolina R. Moreno, Rodrigo N. Ramos, Mariana O. Diniz, Laís Helena T.M. de Andrade, Daniela S. Rosa, José Alexandre M. Barbuto, Silvia B. Boscardin and Luís Carlos S. Ferreira
Mol Cancer Ther August 17 2017 DOI: 10.1158/1535-7163.MCT-17-0071
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Molecular Cancer Therapeutics
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