Room: Track 3
Purpose: Cancer vaccine development has been hampered by the paucity of universal tumor-associated antigens and the difficulty in isolating and preparing individualized vaccines ex vivo. In-situ vaccination seeks to circumvent this limitation by stimulating an immune response in situ (at the tumor site) exploiting tumor-associated antigens with and without radiotherapy. The purpose of this study was to investigate the potential of caflanone (FBL-03G), a non-psychoactive cannabis derivative, as an in-situ vaccine delivered from smart radiotherapy biomaterials.
Methods: Smart radiotherapy biomaterials (SRBs), which can be used in place of fiducial markers or beacons were developed using Poly (lactic-co-glycolic)-acid, an FDA approved polymer, loaded with caflanone for sustained delivery in tumors. Caflanone, was isolated as a flavonoid from a non-cannabinoid rich fraction from Cannabis sativa. 200 µg of caflanone drug was loaded in SRBs and then administered into LSL-Kras; p53+/floxed, Pdx-cre (KPC) heterotopic (subcutaneous) and/or orthotopic tumors in mice. Tumor volume and mice survival were assessed over time as well as histology studies conducted to assess the immune cell population involved in response to caflanone.
Results: The results revealed that sustained delivery of caflanone from the SRBs significantly delayed tumor growth by about 3-fold compared to control group. Furthermore, immunofluorescence results reveal higher CD4/CD8+ T-cells infiltration in treated cohorts compared to controls. Mice treated with SRB_FBL-03G showed significant survival p < 0.05 up to 60 days post treatment.
Conclusion: The findings highlight the potential of caflanone for in-situ vaccination with and without radiotherapy in pancreatic cancer treatment. Response in both treated and untreated tumors was consistent with findings in immune cell populations and suggest the mechanism of action of caflanone to be immune system mediated. The results provide impetus for further studies developing in-situ vaccination approaches with image-guided radiotherapy for treatment of pancreatic cancer.