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 Blood, 1 February 2007, Vol. 109, No. 3, pp. 1185-1192.
Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-07-034017.

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Submitted July 7, 2006
Accepted September 18, 2006

Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities

Julie A McEarchern, Ezogelin Oflazoglu, Leigh Francisco, Charlotte F McDonagh, Kristine A Gordon, Ivan Stone, Kerry Klussman, Eileen Turcott, Nico van Rooijen, Paul Carter, Iqbal S Grewal, Alan F Wahl, and Che-Leung Law*

Seattle Genetics, Inc.
Vrije Universiteit, Netherlands
Trubion Pharmaceuticals Inc.

* Corresponding author; email: claw{at}seagen.com.

Antigens expressed on malignant cells in the absence of significant expression on normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly expressed in hematologic malignancies including non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma. In addition, solid tumors such as renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma, and glioblastoma express high levels of this antigen. To functionally target CD70-expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to contain human IgG1 constant domains. The engineered antibody retained the binding specificity of the murine parent monoclonal antibody and was shown to induce Fc-mediated effector functions including antibody-dependent cellular cytotoxicity, complement dependent cytotoxicity and antibody-dependent cellular phagocytosis in vitro. Further, administration of this antibody significantly prolonged survival of SCID mice bearing CD70+ disseminated human NHL xenografts. Survival of these mice was dependent upon the activity of resident effector cells including neutrophils, macrophages and NK cells. These data suggest that an anti-CD70 antibody, when engineered to contain human IgG1 constant domains, possesses effector cell-mediated antitumor activity and has potential utility for anticancer therapy.


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