Non-clinical safety evaluation of repeated intramuscular administration of the AS15 immunostimulant combined with various antigens in XXXX and @entity5434 .

@entity137 @entity70662 @entity1133 @entity5 @entity4 @entity5434 @entity648 @entity95 @entity1011
UNASSIGNED: Combination of tumor antigens with immunostimulants is a promising approach in @entity5 immunotherapy. We assessed animal model @entity137 of AS15 combined with various tumor antigens: @entity70662 ( @entity95 ), or p501, dHER2 and recPRAME ( @entity5434 ), administered in seven or 20 dose regimens versus a saline control. Clinical and ophthalmological examinations, followed by extensive post-mortem pathological examinations, were performed on all animals. Blood hematology and biochemistry parameters were also assessed. Antigen-specific antibody titers were determined by enzyme-linked immunosorbent assay. Additional assessments in monkeys included electrocardiography and immunohistochemical evaluations of the p501 expression pattern. Transient increases in body temperature were observed 4 h or 24 h after injections of recPRAME   +   AS15 and dHER2   +   AS15. @entity4 and erythema were observed up to 1 week after most injections of recPRAME   +   AS15 and all injections of dHER2   +   AS15. No treatment-related effects were observed for electrocardiography parameters. Mean fibrinogen levels were significantly higher in all treated groups compared to controls, but no differences could be observed at the end of the treatment-free period. Transient but significant differences in biochemistry parameters were observed post-injection: lower albumin/globulin ratios (p501   +   AS15), and higher @entity648 , @entity1133 and @entity1011 (dHER2   +   AS15). Pathology examinations revealed significant increases in axillary lymph node mean weights (recPRAME   +   AS15) compared to controls. A 100% seroconversion rate was observed in all treated groups, but not in controls. p501 protein expression was observed in prostates of all monkeys from studies assessing p501   +   AS15. These results suggest a favorable safety profile of the AS15-containing candidate vaccines, supporting the use of AS15 for clinical development of potential anticancer vaccines. Copyright    2015 The Authors. Journal of Applied Toxicology Published by John Wiley _ Sons Ltd.
