Despite current therapy, head and neck squamous cell cancers (HNSCCs) arising from various mucosal sites of the upper aero-digestive tract frequently relapse in a loco-regional manner and have a poor prognosis. Our objective was to validate an innovative mucosal route of vaccination using plasmo virus-like particles (pVLPs) in a pre-clinical orthotopic model of HNSCCs.
pVLP-E7, that are plasmid DNA encoding retroviral virus-like particles carrying a truncated E7 oncoprotein from HPV16 as antigen model, were used to vaccinate mice bearing pre-established TC-1 tumors implanted into the buccal mucosa. pVLP-E7 were combined with clinical grade TLR agonists (Imiquimod and CpG-ODN). In this pre-clinical orthotopic model, whose tumor microenvironment resembles to those of human HNSCCs, we tested different mucosal vaccination routes for their ability to elicit efficient immune and anti-tumoral responses.
Mucosal intra-cheek (IC) vaccinations using pVLP-E7, comparatively to intradermic vaccinations (ID), gave rise to higher mobilization of mucosal (CD49a+) CD8+ specific effector T cells in both tumor draining lymph nodes and tumor microenvironment resulting in better anti-tumor effects and in a long-term protection against tumor rechallenge. In vivo CD8 depletion demonstrated that anti-tumoral effects were fully dependent upon the presence of CD8+ T cells.
Validation of IC mucosal vaccinations with pVLPs combined with adjuvants using a pre-clinical orthotopic model of HNSCC provide valuable pre-clinical data to rapidly envision the use of such therapeutic vaccines and to implement a clinical trial in patients with HNSCCs, inasmuch as vaccinal components and adjuvants can be easily obtained as clinical grade reagents.