Immune Netw.
2005 Sep;5(3):172-178. 10.4110/in.2005.5.3.172.
Enhanced CEA-specific Immune Responses by Tat-LLO Fusion Protein
- Affiliations
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- 1Department of Microbiology and Immunology, College of Medicine, The Catholic University of Korea, Seoul, Korea. kimtg@catholic.ac.kr
- 2Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
- KMID: 2150613
- DOI: http://doi.org/10.4110/in.2005.5.3.172
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.
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