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: B-R Kim, E-K Yang, D-Y Kim, S-H Kim, D-C Moon, J-H Lee, H-J Kim, J-C Lee
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 167 Issue 1 Pg. 73-83 (Jan 2012) ISSN: 1365-2249 [Electronic] England
• PMID: 22132887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Chemical References

• Antigens, Neoplasm
• Bacterial Outer Membrane Proteins
• Cancer Vaccines
• Interleukin-2
• Recombinant Fusion Proteins
• Tumor Necrosis Factor-alpha
• OMPA outer membrane proteins
• Interferon-gamma
• CA9 protein, human
• Carbonic Anhydrase IX
• Carbonic Anhydrases

Topics

• Acinetobacter baumannii (genetics, immunology)
• Animals
• Antigens, Neoplasm (genetics, immunology)
• Bacterial Outer Membrane Proteins (genetics, immunology)
• Cancer Vaccines (therapeutic use)
• Carbonic Anhydrase IX
• Carbonic Anhydrases (genetics, immunology)
• Carcinoma, Renal Cell (therapy)
• Cell Line, Tumor (immunology, transplantation)
• Cytotoxicity, Immunologic
• Dendritic Cells (drug effects, immunology, transplantation)
• Drug Screening Assays, Antitumor
• Humans
• Interferon-gamma (metabolism)
• Interleukin-2 (metabolism)
• Kidney Neoplasms (therapy)
• Male
• Mice
• Mice, Inbred BALB C
• Protein Structure, Tertiary
• Recombinant Fusion Proteins (chemistry, immunology, pharmacology)
• Specific Pathogen-Free Organisms
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)