作者: Paul H. Naylor , Karla E. Hernandez , April E. Nixon , Harvey J. Brandwein , Gabriel P. Haas
DOI: 10.1016/J.VACCINE.2010.08.014
关键词:
摘要: Therapeutic cancer vaccines are attractive due to the prospect of specificity and their lack toxicity; however, clinical development has been hampered by several biologic challenges. One most important challenges is relative effective cellular immune adjuvants. Effective physiologic responses characterized local generation a complex cytokine environment that activates regulates multiple cell types. IRX-2 primary cell-derived with physiological levels active components, produced under pharmaceutical standards. The hypothesis amplifies T response defined antigens was assessed in mice measuring cell-specific peptide dominant mouse (NFT) derived from human prostate-specific membrane antigen (PSMA). enhances NFT when were delivered either via irradiated cells expressing PSMA, Incomplete Freund's adjuvant (IFA) or conjugated KLH. activity measured spleen lymph nodes IFN-γ ELISpot and/or secretion over 6 days vivo peptide-specific delayed-type hypersensitivity reaction (DTH). Further more, single administration not as compared 4 9 additional administrations which sufficient enhance antigens. influence on B ovalbumin it used carrier protein ELISA. commercially available combination (MPL+TDM squalene/Tween 80) based literature potent murine systems. In assay superior while also increased antibody titer, adjuvant. Mice immunized exhibited delayed tumor progression following challenge PSMA-expressing cells. These studies demonstrate an immunomodulator preferentially associated Based these studies, candidate for evaluation variety preclinical vaccine delivery systems well trials candidates.