PLGA/PVA nanoparticles to deliver a protein-based cancer vaccine targeting GPC1 for the treatment of pancreatic ductal adenocarcinoma

Introduction: Therapeutic cancer vaccines have been proposed to stimulate an immune response for controlling disease progression and reducing treatment recurrence in cancer, such as pancreatic ductal adenocarcinoma (PDAC). Here, we proposed the use of PLGA/PVA nanoparticles (NPs) as the delivery component of a vaccine constituted by a chimeric protein composed of glypican-1 (GPC1) associated with flagellin (FL) from Salmonella typhi (GPC1-FL) for PDAC treatment. Methods: Subcutaneous and oral vaccination protocols were performed in a PDAC syngeneic mouse model with GPC1-FL PLGA/PVA NPs. Results: In a syngeneic mouse model of human GPC1-expressing PDAC, we showed evidence of immunogenicity of GPC1-FL being capable of eliciting a specific anti-GPC1 IgG antibody response when subcutaneously administered. Moreover, we demonstrated that the use of PLGA/PVA NPs to encapsulate GPC1-FL is capable of increasing immunogenicity of the formulation, as demonstrated by the higher anti-GPC1 IgG titer, also associated with mouse survival increase. Finally, we demonstrated both in vitro and in vivo that the PLGA/PVA NPs are able to protect GPC1-FL during gastrointestinal transit and promote its delivery to the intestinal immune system after oral administration. Conclusions: PLGA/PVA NPs could act as the delivery component of an effective vaccine formulation against GPC1 that could be useful for PDAC treatment.