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Blood, 1 January 2008, Vol. 111, No. 1, pp. 338-343. Prepublished online as a Blood First Edition Paper on September 25, 2007; DOI 10.1182/blood-2007-07-102350. This Article Full Text (PDF) All Versions of this Article: blood-2007-07-102350v1 111/1/338    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Du, X. Articles by Pastan, I. Search for Related Content PubMed PubMed Citation Articles by Du, X. Articles by Pastan, I. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 19, 2007 Accepted September 13, 2007 FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia and B-cell non-Hodgkin's lymphoma as a target of immunotoxins Xing Du, Satoshi Nagata, Tomoko Ise, Maryalice Stetler-Stevenson, and Ira Pastan* Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States * Corresponding author; email: pastani{at}mail.nih.gov. FCRL1 (Fc receptor like 1) is a cell-surface membrane protein belonging to FCRL family and is preferentially expressed on B-cells. To evaluate FcRL1 as an immunotherapy target for B-cell malignancies, we prepared anti-FCRL1 mAbs without cross-reactivity to other FCRL family proteins and analyzed FCRL1 protein expression on malignant cells from patient and on B-cell lines. Frequent FCRL1 expression was observed by flow cytometry on 12 B-cell non-Hodgkin's lymphoma (B-NHL) cell lines and many patient samples: 12 of 14 chronic lymphocytic leukemia (CLL), 7 of 7 follicular lymphoma (FL), 13 of 17 hairy cell leukemia (HCL), and 2 of 3 mantle cell lymphoma (MCL). Two recombinant immunotoxins, E3(Fv)-PE38 and E9(Fv)-PE38, were constructed. Both immunotoxins bound to FCRL1 positive cells with similar affinities (3.4 and 3.2 nM) and were cytotoxic to cell lines, but E9(Fv)-PE38 was 4-20 fold more cytotoxic than E3(Fv)-PE38. The IC50s of E9(Fv)-PE38 on 11 different FCRL1 positive cell lines rang from 1.0 ng/ml to 90 ng/ml and correlate with the FCRL1 expression levels. Our results suggest that anti-FCRL1 immunotoxin E9(Fv)-PE38 exhibits remarkably specific cytotoxicity and merits further evaluation for the treatment of FCRL1 positive malignancies, including CLL, HCL, FL, MCL, and other B-NHL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Nagata, T. Ise, and I. Pastan Fc Receptor-Like 3 Protein Expressed on IL-2 Nonresponsive Subset of Human Regulatory T Cells J. Immunol., June 15, 2009; 182(12): 7518 - 7526. [Abstract] [Full Text] [PDF] J. E. Weldon, L. Xiang, O. Chertov, I. Margulies, R. J. Kreitman, D. J. FitzGerald, and I. Pastan A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity Blood, April 16, 2009; 113(16): 3792 - 3800. [Abstract] [Full Text] [PDF] X. Du, R. Beers, D. J. FitzGerald, and I. Pastan Differential Cellular Internalization of Anti-CD19 and -CD22 Immunotoxins Results in Different Cytotoxic Activity Cancer Res., August 1, 2008; 68(15): 6300 - 6305. [Abstract] [Full Text] [PDF] F. J. Li, S. Ding, J. Pan, M. A. Shakhmatov, E. Kashentseva, J. Wu, Y. Li, S.-j. Soong, N. Chiorazzi, and R. S. Davis FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia Blood, July 1, 2008; 112(1): 179 - 187. [Abstract] [Full Text] [PDF]

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