title: 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.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland. Paul.Walker@hcuge.ch madiha.derouazi@amaltherapeutics.com.
authors.forename: Madiha
authors.initials: M
authors.lastname: Derouazi
authors.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
authors.forename: Wilma
authors.initials: W
authors.lastname: Di Berardino-Besson
authors.affiliation: Amal Therapeutics, Geneva, Switzerland.
authors.forename: Elodie
authors.initials: E
authors.lastname: Belnoue
authors.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoepner
authors.affiliation: University of Toulouse, CNRS 5273, UMR STROMALab, Toulouse, France.
authors.forename: Romy
authors.initials: R
authors.lastname: Walther
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Mahdia
authors.initials: M
authors.lastname: Benkhoucha
authors.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Teta
authors.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Dufour
authors.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Yacoub Maroun
authors.affiliation: Oncovir Inc., Washington, District of Columbia.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Salazar
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Martinvalet
authors.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dietrich
authors.affiliation: Geneva University Hospitals and University of Geneva, Centre of Oncology, Geneva, Switzerland. Paul.Walker@hcuge.ch madiha.derouazi@amaltherapeutics.com.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Walker
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D057846:Cell-Penetrating Peptides / Q000276:immunology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000628:therapy; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology
chemical_list: D019496:Cancer Vaccines; D057846:Cell-Penetrating Peptides; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014614:Vaccines, Synthetic