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Targeting self- and neoepitopes with a modular self-adjuvanting cancer vaccine

Belnoue, Elodie
Mayol, Jean-François
Carboni, Susanna
Di Berardino Besson, Wilma
Nelde, Annika
Stevanovic, Stefan
Santiago-Raber, Marie-Laure
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Published in JCI Insight. 2019, vol. 4, no. 11
Abstract Induction of a potent CD4 and CD8 T-cell response against tumor-specific and tumor-associated antigen is critical for eliminating tumor cells. Recent vaccination strategies have been hampered by an inefficacious and low amplitude immune response. Here we describe a self-adjuvanted chimeric protein vaccine platform to address these challenges, characterized by a multidomain construction incorporating (i) a cell penetrating peptide (CPP) allowing internalization of several multiantigenic Major Histocompatibility Complex (MHC)-restricted peptides within (ii) the multiantigenic domain (Mad) and (iii) a TLR2/4 agonist domain (TLRag). Functionality of the resulting chimeric protein is based on the combined effect of the above-mentioned three different domains for simultaneous activation of antigen presenting cells and antigen cross-presentation, leading to an efficacious multiantigenic and multiallelic cellular immune response. Helper and cytotoxic T-cell responses were observed against model-, neo- and self-antigens, and were highly potent in several murine tumor models. The safety and the immunogenicity of a human vaccine candidate designed for colorectal cancer treatment was demonstrated in a non-human primate model. This newly engineered therapeutic vaccine approach is promising for the treatment of poorly infiltrated tumors that do not respond to currently marketed immunotherapies.
PMID: 31013258
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Other version: https://insight.jci.org/articles/view/127305
Research group Immunobiologie des tumeurs du cerveau (669)
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BELNOUE, Elodie et al. Targeting self- and neoepitopes with a modular self-adjuvanting cancer vaccine. In: JCI Insight, 2019, vol. 4, n° 11. doi: 10.1172/jci.insight.127305 https://archive-ouverte.unige.ch/unige:127234

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Deposited on : 2019-12-02

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