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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3707-3713. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-08-3216. This Article Full Text (PDF) All Versions of this Article: 2004-08-3216v1 105/9/3707    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kawakami, M. Articles by Puri, R. K Search for Related Content PubMed PubMed Citation Articles by Kawakami, M. Articles by Puri, R. K Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 20, 2004 Accepted December 18, 2004 Hodgkin's lymphoma therapy with interleukin-4 receptor-directed cytotoxin in an infiltrating animal model Mariko Kawakami, Koji Kawakami*, Mitomu Kioi, Pamela Leland, and Raj K Puri Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA; Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan * Corresponding author; email: kawakami-k{at}umin.ac.jp. Hodgkin's lymphoma represents unique clinicopathological features because Hodgkin and Reed-Sternberg (H-RS) cells produce a variety of cytokines, express a variety of cytokine receptors, and are surrounded by numerous non-malignant immunoreactive cells. We found that receptors for interleukin-4 (IL-4R) are highly expressed in H-RS cells. To target IL-4R, we utilized a recombinant protein fusing circularly permuted human IL-4 and Pseudomonas exotoxin termed IL4(38-37)-PE38KDEL or IL-4 cytotoxin. The cytotoxic effect of IL-4 cytotoxin on H-RS cell lines was determined to be moderate to high in vitro. We developed an infiltrating model of Hodgkin's disease by injecting an adherent population of HD-MyZ cells subcutaneously into the flanks of beige/nude/X-linked immunodeficient mice. The animal model exhibited spontaneous metastasis of H-RS cells to lymph nodes as well as dissemination to vital organs including the lungs. Intraperitoneal or intratumoral treatment of these mice with IL-4 cytotoxin resulted in regression of the primary tumor mass and a decrease in the incidence of lymph node metastasis. Mice injected with HD-MyZ cells demonstrated 203% prolonged survival (mean survival, 63 days) compared to control (mean survival, 31 days) when they received systemic IL-4 cytotoxin treatment. Because a variety of H-RS cell lines express receptors for IL-4, IL-4 cytotoxin may be a unique agent for the treatment of Hodgkin's lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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