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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Porchia, Bruna F. M. M. ; Moreno, Ana Carolina R. ; Ramos, Rodrigo N. ; Diniz, Mariana O. ; de Andrade, Lais Helena T. M. ; Rosa, Daniela S. ; Barbuto, Jose Alexandre M. ; Boscardin, Silvia B. ; Ferreira, Luis Carlos S.
Total Authors: 9
Document type: Journal article
Source: MOLECULAR CANCER THERAPEUTICS; v. 16, n. 9, p. 1922-1933, SEP 1 2017.
Web of Science Citations: 2
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(+) CD62L(low)). 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(+) CD8 alpha(+) 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. (C) 2017 AACR. (AU)

FAPESP's process: 09/54599-5 - Dendritic cells: integrative elements of the immune system - an applied approach
Grantee:Jose Alexandre Marzagão Barbuto
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/15061-8 - In vivo targetting of HIV- CD4+ t cell epitopes to dendritic cells
Grantee:Daniela Santoro Rosa
Support type: Regular Research Grants
FAPESP's process: 11/51218-0 - Immunotherapy against human papillomavirus (HPV) induced tumors
Grantee:Mariana de Oliveira Diniz
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/20917-0 - Immunotherapy involving the E7 oncoprotein and glycoprotein d (GD) of herpes virus in vaccine formulations designed to control papillomavirus associated tumors
Grantee:Bruna Felício Milazzotto Maldonado Porchia Ribeiro
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/00708-1 - Indoleamine 2,3 dioxygenase in the biology of papillomaviruses-induced tumors: neoadjuvant effects on the immunetherapy of tumors
Grantee:Ana Carolina Ramos Moreno
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 11/08905-7 - Study of mechanisms envolved in modulation of t lymphocyte response against tumor antigens by dendritic cells derived from cancer patients monocytes
Grantee:Rodrigo Nalio Ramos
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/16505-0 - Indoleamine 2,3 dioxygenase in the biology of papillomaviruses-induced tumors: neoadjuvant effects on the immunetherapy of tumors
Grantee:Ana Carolina Ramos Moreno
Support type: Research Grants - Young Investigators Grants