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

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

Galliverti, Gabriele  
•
Tichet, Melanie  
•
Domingos-Pereira, Sonia
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November 1, 2018
Cancer Immunology Research

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+ 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(+) T cells with increased effector functions than unconjugated free E7LP. At the tumor site, NP-E7LP prompted a robust infiltration of CD8(+) T cells that was not accompanied by concomitant accumulation of regulatory T cells (Tregs), resulting in a higher CD8(+) 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. (C) 2018 AACR.

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Type
research article
DOI
10.1158/2326-6066.CIR-18-0166
Web of Science ID

WOS:000448923500003

Author(s)
Galliverti, Gabriele  
•
Tichet, Melanie  
•
Domingos-Pereira, Sonia
•
Hauert, Sylvie  
•
Nardelli-Haefliger, Denise
•
Swartz, Melody A.  
•
Hanahan, Douglas  
•
Wullschleger, Stephan  
Date Issued

2018-11-01

Publisher

AMER ASSOC CANCER RESEARCH

Published in
Cancer Immunology Research
Volume

6

Issue

11

Start page

1301

End page

1313

Subjects

Oncology

•

Immunology

•

cervical-cancer patients

•

type-16 transgenic mice

•

t-cell-activation

•

squamous carcinogenesis

•

antigen presentation

•

established tumors

•

immune-response

•

dendritic cells

•

long peptides

•

lymph-node

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
CMSO  
LCSB  
Available on Infoscience
December 13, 2018
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/152207
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