title: Generation of anti-tumour immune response using dendritic cells pulsed with carbonic anhydrase IX-Acinetobacter baumannii outer membrane protein A fusion proteins against renal cell carcinoma.
abstract: Carbonic anhydrase IX (CA9), a specific molecular marker for renal cell carcinoma (RCC), serves as a potential target for RCC-specific immunotherapy using dendritic cells (DCs). However, pulsing of DCs with CA9 alone is not sufficient for generation of a therapeutic anti-tumour immune response against RCC. In this study, in order to generate a potent anti-tumour immune response against RCC, we produced recombinant CA9-Acinetobacter baumannii outer membrane protein A (AbOmpA) fusion proteins, designated CA9-AbOmpA, and investigated the ability of DCs pulsed with CA9-AbOmpA fusion proteins in a murine renal cell carcinoma (RENCA) model. A recombinant CA9-AbOmpA fusion protein was composed of a unique proteoglycan-related region of CA9 (1-120 amino acids) fused at the C-terminus with transmembrane domain of AbOmpA (1-200 amino acids). This fusion protein was capable of inducing DC maturation and interleukin (IL)-12 production in DCs. Interaction of DCs pulsed with CA9-AbOmpA fusion proteins with naive T cells stimulated secretion of IL-2, interferon (IFN)-γ and tumour necrosis factor (TNF)-α in T cells. Lymphocytes harvested from mice immunized with DCs pulsed with CA9-AbOmpA fusion proteins secreted IFN-γ and showed a specific cytotoxic activity against CA9-expressing RENCA (RENCA-CA9) cells. Administration of CA9-AbOmpA-pulsed DC vaccine suppressed growth of RENCA-CA9 cells in mice with an established tumour burden. These results suggest that DCs pulsed with CA9-AbOmpA fusion proteins generate a specific anti-tumour immune response against RCC, which can be utilized in immunotherapy of RCC.
authors: Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea.
authors: B-R
authors: BR
authors: Kim
authors: E-K
authors: EK
authors: Yang
authors: D-Y
authors: DY
authors: Kim
authors: S-H
authors: SH
authors: Kim
authors: D-C
authors: DC
authors: Moon
authors: J-H
authors: JH
authors: Lee
authors: H-J
authors: HJ
authors: Kim
authors: J-C
authors: JC
authors: Lee
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D045744:Cell Line, Tumor / Q000276:immunology / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C078167:OMPA outer membrane proteins; D007371:Interferon-gamma; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases