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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1955-1962. Prepublished online as a Blood First Edition Paper on October 6, 2005; DOI 10.1182/blood-2005-05-2177. This Article Full Text (PDF) All Versions of this Article: 2005-05-2177v1 107/5/1955    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 Pogge von Strandmann, E. Articles by Engert, A. Search for Related Content PubMed PubMed Citation Articles by Pogge von Strandmann, E. Articles by Engert, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 31, 2005 Accepted September 18, 2005 A novel bispecific protein (ULBP2-BB4) targeting the NKG2D receptor on natural killer (NK) cells and CD138 activates NK cells and has potent antitumor activity against human multiple myeloma in vitro and in vivo Elke Pogge von Strandmann, Hinrich P. Hansen, Katrin S. Reiners, Roland Schnell, Peter Borchmann, Sabine Merkert, Venkateswara R. Simhadri, Andreas Draube, Marcel Reiser, Ingvill Purr, Michael Hallek, and Andreas Engert* Department I for Internal Medicine, Laboratory of Immunotherapy, University Hospital Cologne, Cologne, Germany * Corresponding author; email: az.engert{at}uni-koeln.de. The inability of the immune system to recognize and kill malignant plasma cells in patients with multiple myeloma (MM) has been attributed in part to the ineffective activation of natural killer (NK) cells. In order to activate and target NK cells to the malignant cells in MM we designed a novel recombinant bispecific protein (ULBP2-BB4). While ULBP2 binds the activating NK receptor NKG2D, the BB4 moiety binds to CD138, which is overexpressed on a variety of malignancies including MM. ULBP2-BB4 strongly activated primary NK cells as demonstrated by a significant increase in IFN-g secretion. In vitro, ULBP2-BB4 enhanced the NK-mediated lysis of two CD138+ human multiple myeloma cell lines, U-266 and RPMI-8226, and of primary malignant plasma cells in the allogenic and autologous setting. Moreover, in a nude mouse model with subcutaneously growing RPMI-8226 cells, the co-therapy with ULBP-BB4 and human peripheral blood lymphocytes abrogated the tumor growth. These data suggest potential clinical use of this novel construct in patients with MM. The use of recombinant NK receptor ligands that target NK cells to tumor cells might offer new approaches for other malignancies provided a tumor antigen-specific antibody is available. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Boll, F. Eltaib, K. S. Reiners, B. von Tresckow, S. Tawadros, V. R. Simhadri, F. J. Burrows, K. Lundgren, H. P. Hansen, A. Engert, et al. Heat Shock Protein 90 Inhibitor BIIB021 (CNF2024) Depletes NF-{kappa}B and Sensitizes Hodgkin's Lymphoma Cells for Natural Killer Cell-Mediated Cytotoxicity Clin. Cancer Res., August 15, 2009; 15(16): 5108 - 5116. [Abstract] [Full Text] [PDF] C. Germain, E. Campigna, I. Salhi, S. Morisseau, I. Navarro-Teulon, J.-P. Mach, A. Pelegrin, and B. Robert Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein Protein Eng. Des. Sel., November 1, 2008; 21(11): 665 - 672. [Abstract] [Full Text] [PDF] P. Lunghi, N. Giuliani, L. Mazzera, G. Lombardi, M. Ricca, A. Corradi, A. M. Cantoni, L. Salvatore, R. Riccioni, A. Costanzo, et al. Targeting MEK/MAPK signal transduction module potentiates ATO-induced apoptosis in multiple myeloma cells through multiple signaling pathways Blood, September 15, 2008; 112(6): 2450 - 2462. [Abstract] [Full Text] [PDF] W. Cao, X. Xi, Z. Wang, L. Dong, Z. Hao, L. Cui, C. Ma, and W. He Four novel ULBP splice variants are ligands for human NKG2D Int. Immunol., August 1, 2008; 20(8): 981 - 991. [Abstract] [Full Text] [PDF] J. B. Knight, S. A. Halperin, K. A. West, and S. F. Lee Expression of a Functional Single-Chain Variable-Fragment Antibody against Complement Receptor 1 in Streptococcus gordonii Clin. Vaccine Immunol., June 1, 2008; 15(6): 925 - 931. [Abstract] [Full Text] [PDF] C. Carlo-Stella, A. Guidetti, M. Di Nicola, C. Lavazza, L. Cleris, D. Sia, P. Longoni, M. Milanesi, M. Magni, Z. Nagy, et al. IFN-{gamma} Enhances the Antimyeloma Activity of the Fully Human Anti-Human Leukocyte Antigen-DR Monoclonal Antibody 1D09C3 Cancer Res., April 1, 2007; 67(7): 3269 - 3275. [Abstract] [Full Text] [PDF] J. North, I. Bakhsh, C. Marden, H. Pittman, E. Addison, C. Navarrete, R. Anderson, and M. W. Lowdell Tumor-Primed Human Natural Killer Cells Lyse NK-Resistant Tumor Targets: Evidence of a Two-Stage Process in Resting NK Cell Activation J. Immunol., January 1, 2007; 178(1): 85 - 94. [Abstract] [Full Text] [PDF]

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