Virulizin® induces production of IL-17E to enhance antitumor activity by recruitment of eosinophils into tumors

Virulizin ® has demonstrated strong antitumor efficacy in a variety of human tumor xenograft models including melanoma, pancreatic cancer, breast cancer, ovarian cancer and prostate cancer. Our previous studies have demonstrated that macrophages, NK cells, and cytokines are important in the antitumo...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2008-12, Vol.57 (12), p.1757-1769
Main Authors: Benatar, Tania, Cao, Ming Y., Lee, Yoon, Li, Hui, Feng, Ningping, Gu, Xiaoping, Lee, Vivian, Jin, Hongnan, Wang, Ming, Der, Sandy, Lightfoot, Jeff, Wright, Jim A., Young, Aiping H.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - therapeutic use
Animals
Antibodies
Antineoplastic agents
Antineoplastic Agents - therapeutic use
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Bile
Biological and medical sciences
Blotting, Western
Cancer Research
Chemotaxis, Leukocyte - drug effects
Cytokines
Cytotoxicity
Electrophoresis, Gel, Two-Dimensional
Enzyme-Linked Immunosorbent Assay
Eosinophils - drug effects
Flow Cytometry
Humans
Immune system
Immunology
Immunotherapy
Interleukin-17 - biosynthesis
Medical sciences
Medicine
Medicine & Public Health
Melanoma
Melanoma, Experimental - drug therapy
Mice
Oncology
Original
Original Article
Ovarian cancer
Pharmacology. Drug treatments
Prostate
R&D
Research & development
Reverse Transcriptase Polymerase Chain Reaction
Tissue Extracts - therapeutic use
Tumors
Xenograft Model Antitumor Assays
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Summary:Virulizin ® has demonstrated strong antitumor efficacy in a variety of human tumor xenograft models including melanoma, pancreatic cancer, breast cancer, ovarian cancer and prostate cancer. Our previous studies have demonstrated that macrophages, NK cells, and cytokines are important in the antitumor mechanism of Virulizin ® . Virulizin ® treatment of tumor bearing mice results in the expansion as well as increased activity of monocytes/macrophages and production of cytokines IL-12 and TNFα and activation of NK cells. In this study we show that the inflammatory cytokine IL-17E (IL-25) is induced by Virulizin ® treatment and is part of its antitumor mechanism. IL-17E is a proinflammatory cytokine, which induces a T H 2 type immune response, associated with eosinophil expansion and infiltration into mucosal tissues. IL-17E was increased in sera of Virulizin ® -treated mice bearing human melanoma xenografts, compared to saline-treated controls, as shown by 2D gel electrophoresis and ELISA. Treatment of splenocytes in vitro with Virulizin ® resulted in increased IL-17E mRNA expression, which peaked between 24 and 32 h post-stimulation. Both in vitro and in vivo experiments demonstrated that B cells produced IL-17E in response to Virulizin ® treatment. Furthermore, Virulizin ® treatment in vivo resulted in increased blood eosinophilia and eosinophil infiltration into tumors. Finally, injection of recombinant IL-17E showed antitumor activity towards xenografted tumors, which correlated with increased eosinophilia in blood and tumors. Taken together, these results support another antitumor mechanism mediated by Virulizin ® , through induction of IL-17E by B cells, leading to recruitment of eosinophils into tumors, which may function in parallel with macrophages and NK cells in mediating tumor destruction.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-008-0502-9