The delivery of stimulatory signals to dendritic cells (DCs) in the tumor microenvironment could be an effective means to break
tumor-induced tolerance. The work presented here evaluates the immunostimulatory properties of
pathogen-associated molecular patterns (
PAMPs), microbial molecules which bind
Toll-like receptors and deliver activating signals to immune cells, when expressed in
tumor cells using adenoviral (Ad) vectors. In vitro, transduction of A549
tumor cells with Ad vectors expressing either
flagellin from Listeria monocytogenes or P40
protein from Klebsiella pneumoniae induced the maturation of human monocyte-derived DCs in co-cultures. In mixed lymphocyte reactions (MLRs), Ad-
flagellin and Ad-P40 transduction of
tumor cells stimulated lymphocyte proliferation and the secretion of IFN-gamma. In vivo, these vectors were used either as stand-alone
immunoadjuvants injected intratumorally or as
vaccine adjuvants combined with a
tumor antigen-expressing vector. When Ad-
PAMPs were administered intratumorally to mice bearing subcutaneous syngeneic B16F0-CAR (cocksackie-
adenovirus receptor)
melanomas,
tumor progression was transiently inhibited by Ad-P40. In a therapeutic
vaccine setting, the combination of Ad-MUC1 and Ad-
PAMP vectors injected subcutaneously delayed the growth of implanted RenCa-MUC1
tumors and improved
tumor rejection when compared with vaccination with Ad-MUC1 alone. These results suggest that Ad-
PAMPs could be effective
immunoadjuvants for
cancer immunotherapy.