Ccr4-expressing T Cell Tumors Can Be Specifically Controlled Via Delivery of Toxins to Chemokine Receptors.
From: Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Aug 2007
- ISSN: 0022-1767
- Volume: 179
- Issue: 3
- Pages: 1996-2004
- Medium: Print
- Language: English
- Citation (JAMA): Baatar Dolgor, Olkhanud Purevdorj, Newton Dianne, et al. Ccr4-expressing T Cell Tumors Can Be Specifically Controlled Via Delivery of Toxins to Chemokine Receptors.. J. Immunol. Aug 2007;179:1996-2004
Abstract
Expression of chemokine receptors by tumors, specifically CCR4 on cutaneous T cell lymphomas, is often associated with a poor disease outcome. To test the hypothesis that chemokine receptor-expressing tumors can be successfully controlled by delivering toxins through their chemokine receptors, we have generated fusion proteins designated chemotoxins: chemokines fused with toxic moieties that are nontoxic unless delivered into the cell cytosol. We demonstrate that chemokines fused with human RNase eosinophil-derived neurotoxin or with a truncated fragment of Pseudomonas exotoxin 38 are able to specifically kill tumors in vitro upon internalization through their respective chemokine receptors. Moreover, treatment with the thymus and activation-regulated chemokine (CCL17)-expressing chemotoxin efficiently eradicated CCR4-expressing cutaneous T cell lymphoma/leukemia established in NOD-SCID mice. Taken together, this work represents a novel concept that may allow control of growth and dissemination of tumors that use chemokine receptors to metastasize and circumvent immunosurveillance.
Mesh Headings (Keywords): ADP Ribose Transferases, Animals, Antineoplastic Agents, Bacterial Toxins, Cell Death, Cell Line, Cell Line, Tumor, Chemokine CCL17, Chemokines, CC, Cytotoxicity, Immunologic, Eosinophil-Derived Neurotoxin, Exotoxins, Female, Humans, Immunotoxins, Leukemia-Lymphoma, Adult T-Cell, Mice, Mice, Inbred NOD, Mice, SCID, Neoplasm Recurrence, Local, Receptors, CCR4, Receptors, Chemokine, Viral Proteins, Virulence Factors
Check for Full Text / PubMed Unique Identifier (PMID): 17641067
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