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

作者：Derouazi Madiha; Di Berardino Besson Wilma; Belnoue Elodie; Hoepner Sabine; Walther Romy; Benkhoucha Mahdia; Teta Patrick; Dufour Yannick; Maroun Celine Yacoub; Salazar Andres M; Martinvalet Denis; Dietrich Pierre Yves; Walker Paul R^*

来源：Cancer Research, 2015, 75(15): 3020-3031.

DOI：10.1158/0008-5472.CAN-14-3017

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.

• 出版日期2015-8-1