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Cancer Res. 2015 Aug 1;75(15):3020-31. doi: 10.1158/0008-5472.CAN-14-3017. Epub 2015 Jun 26.

Novel Cell-Penetrating Peptide-Based Vaccine Induces Robust CD4+ and CD8+ T Cell-Mediated Antitumor Immunity.

Author information

1
Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland. Paul.Walker@hcuge.ch madiha.derouazi@amaltherapeutics.com.
2
Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
3
Amal Therapeutics, Geneva, Switzerland.
4
University of Toulouse, CNRS 5273, UMR STROMALab, Toulouse, France.
5
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
6
Oncovir Inc., Washington, District of Columbia.
7
Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.

Abstract

Vaccines that can coordinately induce multi-epitope T cell-mediated immunity, T helper functions, and immunologic memory may offer effective tools for cancer immunotherapy. Here, we report the development of a new class of recombinant protein cancer vaccines that deliver different CD8(+) and CD4(+) T-cell epitopes presented by MHC class I and class II alleles, respectively. In these vaccines, the recombinant protein is fused with Z12, a novel cell-penetrating peptide that promotes efficient protein loading into the antigen-processing machinery of dendritic cells. Z12 elicited an integrated and multi-epitopic immune response with persistent effector T cells. Therapy with Z12-formulated vaccines prolonged survival in three robust tumor models, with the longest survival in an orthotopic model of aggressive brain cancer. Analysis of the tumor sites showed antigen-specific T-cell accumulation with favorable modulation of the balance of the immune infiltrate. Taken together, the results offered a preclinical proof of concept for the use of Z12-formulated vaccines as a versatile platform for the development of effective cancer vaccines.

PMID:
26116496
DOI:
10.1158/0008-5472.CAN-14-3017
[Indexed for MEDLINE]
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