Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer.

Details

Serval ID
serval:BIB_12931D59EDB4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer.
Journal
Molecular Cancer Therapeutics
Author(s)
Mondini M., Nizard M., Tran T., Mauge L., Loi M., Clémenson C., Dugue D., Maroun P., Louvet E., Adam J., Badoual C., Helley D., Dransart E., Johannes L., Vozenin M.C., Perfettini J.L., Tartour E., Deutsch E.
ISSN
1538-8514 (Electronic)
ISSN-L
1535-7163
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
14
Number
6
Pages
1336-1345
Language
english
Abstract
There is growing interest in the association of radiotherapy and immunotherapy for the treatment of solid tumors. Here, we report an extremely effective combination of local irradiation (IR) and Shiga Toxin B (STxB)-based human papillomavirus (HPV) vaccination for the treatment of HPV-associated head and neck squamous cell carcinoma (HNSCC). The efficacy of the irradiation and vaccine association was tested using a model of HNSCC obtained by grafting TC-1/luciferase cells at a submucosal site of the inner lip of immunocompetent mice. Irradiation and the STxB-E7 vaccine acted synergistically with both single and fractionated irradiation schemes, resulting in complete tumor clearance in the majority of the treated mice. A dose threshold of 7.5 Gy was required to elicit the dramatic antitumor response. The combined treatment induced high levels of tumor-infiltrating, antigen-specific CD8(+) T cells, which were required to trigger the antitumor activity. Treatment with STxB-E7 and irradiation induced CD8(+) T-cell memory, which was sufficient to exert complete antitumor responses in both local recurrences and distant metastases. We also report for the first time that a combination therapy based on local irradiation and vaccination induces an increased pericyte coverage (as shown by αSMA and NG2 staining) and ICAM-1 expression on vessels. This was associated with enhanced intratumor vascular permeability that correlated with the antitumor response, suggesting that the combination therapy could also act through an increased accessibility for immune cells. The combination strategy proposed here offers a promising approach that could potentially be transferred into early-phase clinical trials.
Keywords
Actins/metabolism, Animals, Antigens/metabolism, CD8-Positive T-Lymphocytes/drug effects, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/administration & dosage, Cancer Vaccines/immunology, Cell Line, Combined Modality Therapy, Female, Flow Cytometry, Fluorescent Antibody Technique, Head and Neck Neoplasms/complications, Head and Neck Neoplasms/immunology, Intercellular Adhesion Molecule-1/metabolism, Mice, Inbred C57BL, Muscle, Smooth/chemistry, Papillomavirus Infections/complications, Papillomavirus Infections/immunology, Papillomavirus Vaccines/administration & dosage, Papillomavirus Vaccines/immunology, Pericytes/drug effects, Pericytes/metabolism, Proteoglycans/metabolism, Radiotherapy/methods, Shiga Toxins/immunology, Vaccination/methods
Pubmed
Web of science
Open Access
Yes
Create date
24/08/2015 17:51
Last modification date
20/08/2019 13:40
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