title: A chemically induced vaccine strategy for prostate cancer.
abstract: Here we report the design and evaluation of a bifunctional, small molecule switch that induces a targeted immune response against tumors in vivo. A high affinity ligand for prostate specific membrane antigen (PSMA) was conjugated to a hapten that binds dinitrophenyl (DNP)-specific antibodies. When introduced into hu-PBL-NOD/SCID mice previously immunized with a KLH-DNP immunogen, this conjugate induced a targeted antibody-dependent cellular cytotoxicity (ADCC) response to PSMA-expressing tumor cells in a mouse xenograft model. The ability to create a small molecule inducible antibody response against self-antigens using endogenous non-autoreactive antibodies may provide advantages over the autologous immune response generated by conventional vaccines in certain therapeutic settings.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Dubrovska
authors.forename: Chanhyuk
authors.initials: C
authors.lastname: Kim
authors.forename: Jimmy
authors.initials: J
authors.lastname: Elliott
authors.forename: Weijun
authors.initials: W
authors.lastname: Shen
authors.forename: Tun-Hsun
authors.initials: TH
authors.lastname: Kuo
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Koo
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Tove
authors.initials: T
authors.lastname: Tuntland
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.forename: Todd
authors.initials: T
authors.lastname: Groessl
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gorney
authors.forename: Teresa
authors.initials: T
authors.lastname: Ramirez-Montagut
authors.forename: David A
authors.initials: DA
authors.lastname: Spiegel
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Cho
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
mesh_terms: D019297:2,4-Dinitrophenol / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D019496:Cancer Vaccines / Q000737:chemistry* / Q000276:immunology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D001324:Autoantigens; D019496:Cancer Vaccines; D008024:Ligands; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D019297:2,4-Dinitrophenol