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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.

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Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
Amal Therapeutics, Geneva, Switzerland.
University of Toulouse, CNRS 5273, UMR STROMALab, Toulouse, France.
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Oncovir Inc., Washington, District of Columbia.
Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.


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.

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