Multi-peptide cancer immunotherapy in combination with sorafenib

Abstract

Abstract Background Little is known why most of the cancer immunotherapies failed despite good results in pre-clinical studies. We believe that if we focus on clinically relevant multi-proteins to immune-target simultaneously in combination with drugs with potential immune properties we may improve the clinical outcomes. Methods 12 proteins overexpressed in several human tumors and associated with prognosis were identified. Indirect ELISA (IgA+ IgM + IgG) and ELISPOT was used to evaluate immunity proteins in 50 cancer patients and 50 controls. Immunohistochemistry (IHC) staining was done for proteins and CD8 T-cell quantitation. Peptides that were highly immunogenic by ELISA and ELISPOT were formulated into multi-peptide immunotherapy and with low dose of oral sorafenib. Patients treated with active progressive disease 6 months, 12 times were monitored biweekly to evaluate the immune response. Results Serum responses for all positive antigens were significantly elevated in advanced cancer patient sera when compared to donor controls (Bcl-2 p=0.001, survivin p=0.0001, EGFR P=0.005, Fascin-1 p=0.0001, Sox2 p<0.0002), RCAS1 p= 0.004, VCP = 0.05 and Ape-1 (p=0.0001). ELISPOT screening yielded epitopes that were immunogenic in advanced cancer patients. Metastatic areas of liver and lungs in advanced cancer patients were significantly inhibited after treatment with the multi-peptide immunotherapy and sorafenib. Discussion Advanced cancer is still immunogenic and overexpressed proteins involved in clinical relevant pathways can serve as specific active immunogens. These data could be the proof of principle for the development of multi-peptide immunotherapy in combo with drugs with immune properties such as sorafenib.