The Dendritic Cell-based Vaccine PROTEXI leverages Antiviral CD4 T cell Memory to boost anti-tumor immune responses in mice
Menée à l'aide notamment de modèles murins de mélanome et de cancer mammaire ainsi que de cellules dendritiques dérivées de sang humain, cette étude met en évidence l'intérêt, pour renforcer les réponses immunitaires antitumorales, d'un vaccin à base de cellules dendritiques co-présentant des épitopes de la protéine Spike du virus SARS-CoV-2 (ciblés par les lymphocytes T CD4+) et des épitopes tumoraux (PRAME et MAGE-A3 ciblés par les lymphocytes T CD8+)
The efficacy of dendritic cell (DC) cancer vaccines is linked to poor immunogenicity of tumor-associated antigens and failure to elicit robust MHC class II-restricted CD4⁺ T-cell responses. Here, we introduce PROTEXI, a DC vaccine platform that optimizes tumor immunity by co-presenting tumor-specific CD8⁺ T-cell epitopes alongside CD4⁺ T helper epitopes from the SARS-CoV-2 Spike protein, leveraging widespread anti-viral immunity. In preclinical mouse models of melanoma and breast cancer, PROTEXI significantly reduces tumor growth and improves survival by promoting robust T cell infiltration into immune-cold tumors, increasing cytotoxic T cell responses via epitope spreading, and activating genes linked to optimal DC, NK cell, and T cell function. Furthermore, PROTEXI elicits superior responses when combined with other immunotherapy agents in models of therapy-resistant tumors. Finally, in a humanized mouse model of melanoma, PROTEXI vaccine co-presenting CD4⁺ T-specific Spike epitopes with CD8⁺ T cell-restricted PRAME and MAGE-A3 antigens, significantly reduces tumor burden. Thus, these data underscore the potential of harnessing pre-existing viral-specific immunity to enhance the efficacy of DC vaccines in immune-cold tumors.
Nature Communications , article en libre accès, 2026