Nanoparticle Conjugation of Human Papillomavirus 16 E7-long Peptides Enhances Therapeutic Vaccine Efficacy against Solid Tumors in Mice.

Details

Serval ID
serval:BIB_72C1FA3ADF43
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nanoparticle Conjugation of Human Papillomavirus 16 E7-long Peptides Enhances Therapeutic Vaccine Efficacy against Solid Tumors in Mice.
Journal
Cancer immunology research
Author(s)
Galliverti G., Tichet M., Domingos-Pereira S., Hauert S., Nardelli-Haefliger D., Swartz M.A., Hanahan D., Wullschleger S.
ISSN
2326-6074 (Electronic)
ISSN-L
2326-6066
Publication state
Published
Issued date
11/2018
Peer-reviewed
Oui
Volume
6
Number
11
Pages
1301-1313
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Treatment of patients bearing human papillomavirus (HPV)-related cancers with synthetic long-peptide (SLP) therapeutic vaccines has shown promising results in clinical trials against premalignant lesions, whereas responses against later stage carcinomas have remained elusive. We show that conjugation of a well-documented HPV-E7 SLP to ultra-small polymeric nanoparticles (NP) enhances the antitumor efficacy of therapeutic vaccination in different mouse models of HPV <sup>+</sup> cancers. Immunization of TC-1 tumor-bearing mice with a single dose of NP-conjugated E7LP (NP-E7LP) generated a larger pool of E7-specific CD8 <sup>+</sup> T cells with increased effector functions than unconjugated free E7LP. At the tumor site, NP-E7LP prompted a robust infiltration of CD8 <sup>+</sup> T cells that was not accompanied by concomitant accumulation of regulatory T cells (Tregs), resulting in a higher CD8 <sup>+</sup> T-cell to Treg ratio. Consequently, the amplified immune response elicited by the NP-E7LP formulation led to increased regression of large, well-established tumors, resulting in a significant percentage of complete responses that were not achievable by immunizing with the non-NP-conjugated long-peptide. The partial responses were characterized by distinct phases of regression, stable disease, and relapse to progressive growth, establishing a platform to investigate adaptive resistance mechanisms. The efficacy of NP-E7LP could be further improved by therapeutic activation of the costimulatory receptor 4-1BB. This NP-E7LP formulation illustrates a "solid-phase" antigen delivery strategy that is more effective than a conventional free-peptide ("liquid") vaccine, further highlighting the potential of using such formulations for therapeutic vaccination against solid tumors. Cancer Immunol Res; 6(11); 1301-13. ©2018 AACR.
Keywords
Animals, Antibodies/pharmacology, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/chemistry, Cancer Vaccines/immunology, Cancer Vaccines/pharmacology, Female, Lung Neoplasms/secondary, Mice, Inbred C57BL, Mice, Transgenic, Nanoparticles/chemistry, Neoplasm Recurrence, Local, Neoplasms, Experimental/immunology, Neoplasms, Experimental/mortality, Neoplasms, Experimental/therapy, Papillomavirus E7 Proteins/chemistry, Papillomavirus E7 Proteins/immunology, Papillomavirus E7 Proteins/pharmacology, T-Lymphocytes, Regulatory/immunology, Treatment Outcome, Tumor Necrosis Factor Receptor Superfamily, Member 9/immunology, Vaginal Neoplasms/immunology, Vaginal Neoplasms/pathology, Vaginal Neoplasms/prevention & control
Pubmed
Web of science
Open Access
Yes
Create date
29/08/2018 13:51
Last modification date
26/10/2019 5:09
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