Abstract |
Antibody-targeted superantigen C215Fab-SEA is a fusion protein of staphylococcal enterotoxin A (SEA) and the Fab region of the tumor-reactive C215 mAb. It can trigger CTL against C215 antigen-positive tumor cells and induce tumor-suppressive cytokines. However, the antitumor effect of C215Fab-SEA is not satisfactory because of suboptimal production of Th1 cytokines after repeated administration. Interleukin 18 (IL-18) is a novel cytokine with profound effects on Th1 cellular response. In this study, we showed that adenovirus-mediated intratumoral IL-18 gene transfer strongly improved the therapeutic efficacy of C215Fab-SEA in the pre-established C215 antigen-expressing B16 melanoma murine model. More significant tumor inhibition and prolonged survival time were observed in tumor-bearing mice received combined therapy of C215Fab-SEA and Ad IL-18 than those of mice treated with C215Fab-SEA or AdIL-18 alone. Combination therapy augmented NK and CTL activities of tumor-bearing mice more markedly. The production of IL-2 and IFN-gamma also increased more significantly. More potent antitumor effect of combined therapy was observed in IL-10 KO mice with enhanced Th1 response. Our data demonstrated that the antitumor effect of C215Fab-SEA immunotherapy could be potentiated significantly by combination with intratumoral IL-18 gene transfer through more efficient activation of Th1 immune responses.
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Authors | Q Wang, H Yu, D W Ju, L He, J P Pan, D J Xia, L H Zhang, X Cao |
Journal | Gene therapy
(Gene Ther)
Vol. 8
Issue 7
Pg. 542-50
(Apr 2001)
ISSN: 0969-7128 [Print] England |
PMID | 11319621
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Neoplasm
- Cytokines
- Enterotoxins
- Immunoglobulin Fab Fragments
- Interleukin-18
- Recombinant Fusion Proteins
- Superantigens
- enterotoxin A, Staphylococcal
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Topics |
- Adenoviridae
(genetics)
- Animals
- Antigens, Neoplasm
(immunology)
- Combined Modality Therapy
- Cytokines
(biosynthesis)
- Cytotoxicity, Immunologic
- Enterotoxins
(immunology)
- Female
- Genetic Therapy
(methods)
- Immunoglobulin Fab Fragments
(immunology)
- Interleukin-18
(genetics, immunology)
- Killer Cells, Natural
(immunology)
- Male
- Melanoma, Experimental
(immunology, pathology, therapy)
- Mice
- Mice, Inbred C57BL
- Recombinant Fusion Proteins
(therapeutic use)
- Spleen
(immunology)
- Staphylococcus aureus
(immunology)
- Superantigens
(immunology, therapeutic use)
- Survival Rate
- T-Lymphocytes, Cytotoxic
(immunology)
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