Abstract 186P
Background
Pancreatic adenocarcinoma (PDAC) is projected to significantly increase and become the second cause of cancer-related deaths before 2030. Immunotherapy has revolutionized the treatment of cancer, however, it has failed to show benefits in PDAC treatment. Recent efforts to synergize chemotherapy and immunotherapy have shown promising results in clinical trials. With this rationale, we tested the anti-tumor effect of the combination of the chemotherapeutic agent gemcitabine with a chitosan-based nanoparticle vaccine that contains the immunogenic cancer germline antigen Ny-eso1. Nyeso1-nanovaccine formulation alone or combined with gemcitabine was tested in vitro in mouse PDAC organoids.
Methods
Mouse peripheral blood mononuclear cells (PBMCs) were obtained and stimulated in vitro with Nyeso1- nanovaccine for 48 hours. Mouse PDAC organoids from KPC-orthotopic injected tumors were directly stimulated with Nyeso1-peptide nanovaccine, with respective nanovaccine controls, or indirectly with the Nyeso1- or nanovaccine controls-stimulated PBMCs or with unstimulated PBMCs. Two different gemcitabine concentrations, 0.38 μM and 0.84 μM, were added to the stimulated-PBMCs and the PDAC organoid co-culture system. During 10 days of co-culture, PDAC organoids were imaged using an Incucyte system, and the organoid areas were measured over time in response to treatment.
Results
The addition of Nyeso1-nanovaccine-stimulated PBMCs to the co-culture did not result in an alteration of PDAC organoids growth. However, the combination of Nyeso1-nanovaccine-stimulated PBMCs with gemcitabine led to a total reduction in sizes of PDAC organoids in comparison to PDAC organoids co-cultured with unstimulated- or nanovaccine-formulation stimulated PBMCs. Administration of gemcitabine in the medium of PDAC organoids alone only induced a slight decrease in the size of the PDAC organoids.
Conclusions
Gemcitabine treatment together with Nyeso1-nanovaccine stimulated PBMCs resulted in a synergistic anti-tumor effect in mouse PDAC organoids. Further studies will be carried out to potentiate the antitumor effect of the PBMCs and to analyze antigen-specific response upon nanovaccine treatment.
Legal entity responsible for the study
Frauke Alves.
Funding
European Union.
Disclosure
The author has declared no conflicts of interest.