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Lymphoma

Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics

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Abstract

SGN-30, a monoclonal antibody with activity against CD30+ malignancies, is currently in phase II clinical evaluation for treatment of Hodgkin's disease (HD) and anaplastic large cell lymphoma. The mechanisms underlying SGN-30's antitumor activity were investigated using cDNA array of L540 cells. SGN-30 treatment activated NF-κB and modulation of several messages including the growth regulator p21WAF1/CIP1 (p21) and cellular adhesion marker ICAM-1. p21 protein levels increased coincident with growth arrest and Annexin V/PI staining in treated HD cells. To determine if SGN-30-induced growth arrest would sensitize tumor cells to chemotherapeutics used against HD, L540cy and L428 cells were exposed to SGN-30 in combination with a panel of cytotoxic agents and resultant interactions quantified by the Combination Effects Method. Interactions between SGN-30 and all cytotoxic agents examined were additive or better. These in vitro data translated to increased efficacy of SGN-30 and bleomycin against L540cy tumor xenografts. In addition to direct cell killing, SGN-30 affects growth arrest and drug sensitization through growth regulating and proapoptotic machinery. Importantly, these data suggest that SGN-30 can enhance the efficacy of standard chemotherapies used to treat patients with CD30+ malignancies.

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Author notes

  1. A F Wahl

    Present address: IntraMed, 230 Park Avenue South, New York, NY, 10003, USA

Authors and Affiliations

  1. Department of Molecular Oncology and Immunology, Seattle Genetics, Inc., Bothell, USA

    C G Cerveny, C-L Law, R S McCormick, J S Lenox, K J Hamblett, J A Francisco & A F Wahl

  2. Department of Antibody Technologies, Seattle Genetics, Inc., Bothell, USA

    L E Westendorf, A K Yamane & J M Petroziello

Authors
  1. C G Cerveny
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  2. C-L Law
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  3. R S McCormick
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  4. J S Lenox
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  5. K J Hamblett
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  6. L E Westendorf
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  7. A K Yamane
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  8. J M Petroziello
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  9. J A Francisco
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  10. A F Wahl
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Correspondence to A F Wahl.

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Cerveny, C., Law, CL., McCormick, R. et al. Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics. Leukemia 19, 1648–1655 (2005). https://doi.org/10.1038/sj.leu.2403884

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  • DOI: https://doi.org/10.1038/sj.leu.2403884

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