Enhanced CEA-specific Immune Responses by Tat-LLO Fusion Protein.
- Author:
Soon Aei YI
1
;
Hyun Jung SOHN
;
Chang Hyun KIM
;
Mi Young PARK
;
Seong Taek OH
;
Tai Gyu KIM
Author Information
- Publication Type:Original Article
- Keywords: Carcinoembryonic antigen (CEA); listeriolysin O (LLO); transactivator of transcription (Tat); dendritic cell (DC); cytotoxic T lymphocyte (CTL)
- MeSH: Carcinoembryonic Antigen; Cytoplasm; Dendritic Cells; Epithelial Cells; Humans; Immunization; Immunotherapy; Lymphocytes; T-Lymphocytes; Trans-Activators
- From:Immune Network 2005;5(3):172-178
- CountryRepublic of Korea
- Language:Korean
- Abstract: BACKGROUND: Carcinoembryonic antigen (CEA) is well-known soluble tumor marker frequently detectable in peripheral blood of carcinoma patients and considered as good target for antigen-specific immunotherapy. However, it is known that the induction of immune response to CEA is very difficult because CEA is a self-antigen expressed in fetal cells and weakly expressed in normal colorectal epithelial cells. To enhance anti-tumor immunity specific for CEA, recombinant CEA protein was modified using listeriolysin O (LLO) for endosomal lysis and transactivator of transcription (Tat) domain for transducing extracellular proteins into cytoplasm. METHODS: After immunization using dendritic cells pulsed with Tat-CEA, both Tat-CEA and LLO, and both Tat-CEA and Tat-LLO, antibody titer to CEA and LLO, cytotoxic T lymphocyte activity and the frequency of IFN-gamma producing T lymphocytes were measured. RESULTS: Immunization using DC pulsed with both Tat-CEA and Tat-LLO protein showed the increasement of production of CEA-specific antibody in serum, cytotoxic T lymphocyte activity, the frequency of IFN-gamma secreting T cells, compared with DC pulsed with both Tat-CEA and LLO. Furthermore the ratio of CD8+ T cell to CD4+ T cell among CEA-specific T cells was increased in group pulsed with both Tat-CEA and Tat-LLO. CONCLUSION: These results suggested that DC vaccine using Tat-LLO could be used for the development of effective immunotherapy for the treatment of tumor.
