The paradigm in cancer treatment has shifted over the last decades: while conventional anti-tumoral therapies kill cancer cells, emerging therapies harness key actors of the immune system to promote tumor-specific immune responses. For instance, some therapeutic agents augment dendritic cell (DC) tumor antigen presentation to enhance the priming of tumor-specific cytotoxic T lymphocytes. To that purpose, nanoparticles of various formulations are engineered: they encapsulate an antigen and display a dendritic cell-targeting moiety on their surface, therefore allowing both antigen protection and enhanced dendritic cell-specific delivery.
 
Objectives: Here we developed and characterized a new Virus-Like Particle versatile platform and validated its interest in cancer therapy.
 
Methods: Non-infectious self-assembling antigen-containing nanoparticles were produced in planta from the capsid protein of the Grapevine Fanleaf Virus (VLP_GFLV) (Belval et al., 2016), their surface was functionalized via nanobodies coupled to antibodies targeting DC. In our study, the ovalbumin model antigen was chosen and addressed to Clec9A, a C-type lectin selectively expressed by type 1 conventional DC (the DC subset specialized in antigen cross-presentation) (Caminschi et al., 2008). We evaluated in vitro and in vivo the ability of Clec9A-targeted VLP_GFLV to promote antigen delivery and assessed the subsequent transgenic OVA-specific CD4 and CD8 T lymphocyte activation as well as the endogenic OVA-specific CD8 T lymphocyte activation.
 
Results: We demonstrate that targeting OVA-containing VLP_GFLV to Clec9A efficiently promotes T lymphocyte activation resulting, in vivo, in a specific, systemic and efficient cytotoxic T lymphocyte response. Notably, we found that VLP_GFLV are devoid of self-adjuvanting properties: the co-administration of a DC maturation agent (poly I:C) is therefore required. Finally, we are currently evaluating whether Clec9A-targeted OVA-containing VLP_GFLV provide prophylactic and/or therapeutic protection against OVA-expressing B16 melanoma.
 
Conclusion: VLP_GFLV is a promising platform for anti-tumoral applications as it efficiently promotes a cytotoxic immune response specific for the contained antigen.