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Blood, 15 November 2003, Vol. 102, No. 10, pp. 3737-3742.
Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-02-0515.
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NEOPLASIA
The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma
Peter Borchmann,
John F. Treml,
Hinrich Hansen,
Claudia Gottstein,
Roland Schnell,
Oliver Staak,
Hui-fen Zhang,
Thomas Davis,
Tibor Keler,
Volker Diehl,
Robert F. Graziano, and
Andreas Engert
From the Klinik I für Innere Medizin der Universität Köln, Köln, Germany; and Medarex Inc, Bloomsbury, NJ.
CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma. To overcome the limitations from currently available murine anti-CD30 monoclonal antibodies (mAbs), a new fully human anti-CD30 antibody was generated. Binding properties were evaluated by recombinant CD30 capture enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell-sorter (FACS) flow cytometry. Activity of this new mAb was assessed in vitro using growth inhibition and antibody-dependent cellular cytotoxicity (ADCC) assays on several cell lines. In vivo activity was determined in a solid as well as in a disseminated xenografted model of HL in severe combined immunodeficiency (SCID) mice. The mAb 5F11 showed specific binding to CD30 (cluster A). The ADCC assays indicated dose-dependent lysis of L540 cells when 5F11 was combined with human effector cells. Upon cross-linking in vitro, 5F11 inhibited the growth of CD30-expressing cell lines. In vivo, treatment with 5F11 induced a marked growth delay or even a complete regression of established xenografted HL in SCID mice. In the disseminated HL model, a high proportion of 5F11-treated mice experienced long-term survival. The new human anti-CD30 monoclonal antibody 5F11 shows promise as a means of CD30-targeted immunotherapy of malignant lymphomas. Based on these results, a clinical phase 1 study in patients with refractory CD30+ lymphoma has been initiated. (Blood. 2003;102:3737-3742)
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