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

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.

• Authors: Madiha Derouazi, Wilma Di Berardino-Besson, Elodie Belnoue, Sabine Hoepner, Romy Walther, Mahdia Benkhoucha, Patrick Teta, Yannick Dufour, Céline Yacoub Maroun, Andres M Salazar, Denis Martinvalet, Pierre-Yves Dietrich, Paul R Walker
• Journal: Cancer research (Cancer Res) Vol. 75 Issue 15 Pg. 3020-31 (Aug 01 2015) ISSN: 1538-7445 [Electronic] United States
• PMID: 26116496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Cancer Vaccines
• Cell-Penetrating Peptides
• Epitopes, T-Lymphocyte
• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II
• Vaccines, Synthetic

Topics

• Animals
• Antigen Presentation (immunology)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cancer Vaccines (administration & dosage, immunology, pharmacology)
• Cell-Penetrating Peptides (immunology)
• Cytosol (drug effects, metabolism)
• Dendritic Cells (drug effects, immunology)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Histocompatibility Antigens Class I (immunology, metabolism)
• Histocompatibility Antigens Class II (immunology, metabolism)
• Immunity, Cellular
• Immunization (methods)
• Mice, Inbred C57BL
• Mice, Transgenic
• Neoplasms, Experimental (therapy)
• Th1 Cells (drug effects, immunology)
• Vaccines, Synthetic (immunology, pharmacology)