Transient T cell depletion causes regression of melanoma metastases
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BioMed Central
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Transient T cell depletion causes regression of melanoma metastases Mary Ann Rasku1, Amy L Clem1, Sucheta Telang1, Beverly Taft1, Kelly Gettings1, Hana Gragg1, Daniel Cramer1, Sheron C Lear2, Kelly M McMasters3, Donald M Miller1 and Jason Chesney*1 Address: 1Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA, 2Department of Pathology, University of Louisville School of Medicine, Louisville, KY, USA and 3Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA Email: Mary Ann Rasku - [email protected]; Amy L Clem - [email protected]; Sucheta Telang - [email protected]; Beverly Taft - [email protected]; Kelly Gettings - [email protected]; Hana Gragg - [email protected]; Daniel Cramer - [email protected]; Sheron C Lear - [email protected]; Kelly M McMasters - [email protected]; Donald M Miller - [email protected]; Jason Chesney* - [email protected] * Corresponding author
Published: 11 March 2008 Journal of Translational Medicine 2008, 6:12
doi:10.1186/1479-5876-6-12
Received: 7 January 2008 Accepted: 11 March 2008
This article is available from: http://www.translational-medicine.com/content/6/1/12 © 2008 Rasku et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Cognate immunity against neoplastic cells depends on a balance between effector T cells and regulatory T (Treg) cells. Treg cells prevent immune attack against normal and neoplastic cells by directly suppressing the activation of effector CD4+ and CD8+ T cells. We postulated that a recombinant interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; Ontak) may serve as a useful strategy to deplete Treg cells and break tolerance against neoplastic tumors in humans. Methods: We administered DAB/IL2 (12 μg/kg; four daily doses; 21 day cycles) to 16 patients with metastatic melanoma and measured the effects on the peripheral blood concentration of several T cell subsets and on tumor burden. Results: We found that DAB/IL2 caused a transient depletion of Treg cells as well as total CD4+ and CD8+ T cells (< 21 days). T cell repopulation coincided with the de novo appearance of melanoma antigen-specific CD8+ T cells in several patients as determined by flow cytometry using tetrameric MART-1, tyrosinase and gp100 peptide/MHC conjugates. Sixteen patients received at least one cycle of DAB/IL2 and five of these patients experienced regressions of melanoma metastases as measured by CT and/or PET imaging. One patient experienced a near complete response with the regression of several hepatic and pulmonary metastases coupled to the de nov
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