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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.<\/jats:p>","DOI":"10.4049\/jimmunol.179.3.1996","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T18:56:47Z","timestamp":1397847407000},"page":"1996-2004","source":"Crossref","is-referenced-by-count":28,"title":["CCR4-Expressing T Cell Tumors Can Be Specifically Controlled via Delivery of Toxins to Chemokine Receptors"],"prefix":"10.1093","volume":"179","author":[{"given":"Dolgor","family":"Baatar","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, Gerontology Research Center, National Institute on Aging , Baltimore, MD 21224"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purevdorj","family":"Olkhanud","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Gerontology Research Center, National Institute on Aging , Baltimore, MD 21224"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianne","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Microbiology, SAIC-Frederick, National Cancer Institute , Frederick, MD 21702"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenya","family":"Sumitomo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Gerontology Research Center, National Institute on Aging , Baltimore, MD 21224"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arya","family":"Biragyn","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Gerontology Research Center, National Institute on Aging , Baltimore, MD 21224"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,8,1]]},"reference":[{"key":"2026012809203691000_R1","first-page":"7529","volume-title":"Clin. 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