Next Article in Journal
On the Mechanism of Hyperthermia-Induced BRCA2 Protein Degradation
Next Article in Special Issue
Cancer Immunotherapy: Silencing Intracellular Negative Immune Regulators of Dendritic Cells
Previous Article in Journal
Predicting VTE in Cancer Patients: Candidate Biomarkers and Risk Assessment Models
Previous Article in Special Issue
IL-15 and a Two-Step Maturation Process Improve Bone Marrow-Derived Dendritic Cell Cancer Vaccine
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle

A DNA Vaccine Encoding SA-4-1BBL Fused to HPV-16 E7 Antigen Has Prophylactic and Therapeutic Efficacy in a Cervical Cancer Mouse Model

1
Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey 66460, NL, Mexico
2
The Hiram C. Polk Jr, MD, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY 40202, USA
3
Departamento de Genética Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social (IMSS), Monterrey 64720, NL, Mexico
4
Department of Microbiology and Immunology, Institute of Cellular Therapeutics, University of Louisville, Louisville, KY 40202, USA
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(1), 96; https://doi.org/10.3390/cancers11010096
Received: 26 November 2018 / Revised: 3 January 2019 / Accepted: 8 January 2019 / Published: 15 January 2019
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
  |  
PDF [1524 KB, uploaded 15 January 2019]
  |  

Abstract

The SA-4-1BBL, an oligomeric novel form of the natural ligand for the 4-1BB co-stimulatory receptor of the tumor necrosis factor (TNF) superfamily, as a recombinant protein has potent pleiotropic effects on cells of innate, adaptive, and regulatory immunity with demonstrated therapeutic efficacy in several tumor models. However, the production of soluble form of SA-4-1BBL protein and quality control is time and resource intensive and face various issues pertinent to clinical development of biologics. The present study sought to take advantage of the simplicity and translatability of DNA-based vaccines for the production and delivery of SA-4-1BBL for cancer immune prevention and therapy. A chimeric HPV-16 E7 DNA vaccine (SP-SA-E7-4-1BBL) was constructed that contains the signal peptide (SP) of calreticulin (CRT), streptavidin (SA) domain of SA-4-1BBL, HPV-16 E7 double mutant gene, and the extracellular domain of mouse 4-1BBL. Immunization by gene gun with SP-SA-E7-4-1BBL induced greater prophylactic as well as therapeutic effects in C57BL/6 mice against TC-1 tumor model compared with immunization with E7wt, SP-SA-4-1BBL or reference-positive control CRT-E7wt. The therapeutic efficacy of the DNA vaccine was associated with increased frequency of E7-specific T cells producing interferon (IFN)-γ. Overall, our data suggest that this DNA-based vaccine strategy might represent a translational approach because it provides a simpler and versatile alternative to a subunit vaccine based on SA-4-1BBL and E7 proteins. View Full-Text
Keywords: DNA vaccine; E7; SA-4-1BBL; HPV-16; co-stimulation; IFN-γ; cancer vaccine; T cell responses DNA vaccine; E7; SA-4-1BBL; HPV-16; co-stimulation; IFN-γ; cancer vaccine; T cell responses
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Garza-Morales, R.; Perez-Trujillo, J.J.; Martinez-Jaramillo, E.; Saucedo-Cardenas, O.; Loera-Arias, M.J.; Garcia-Garcia, A.; Rodriguez-Rocha, H.; Yolcu, E.; Shirwan, H.; Gomez-Gutierrez, J.G.; Montes-de-Oca-Luna, R. A DNA Vaccine Encoding SA-4-1BBL Fused to HPV-16 E7 Antigen Has Prophylactic and Therapeutic Efficacy in a Cervical Cancer Mouse Model. Cancers 2019, 11, 96.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top