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In Vitro and in Vivo Antitumor Effect of the Anti-CD26 Monoclonal Antibody 1F7 on Human CD30+ Anaplastic Large Cell T-Cell Lymphoma Karpas 299¹

Departments of Lymphoma/Myeloma [U. A., K. S. M., F. C., N. H. D.], Gastrointestinal Oncology [L. H., C. N., J. L. A.], Molecular Therapeutics [G. B. M., R. L., N. H. D.], and Veterinary Medicine and Surgery [C. S.], M. D. Anderson Cancer Center, Houston, Texas 77030, and Division of Clinical Immunology and AIDS Research Center, Institute of Medical Science, University of Tokyo Tokyo 108-8639, Japan [K. O., C. M.]

CD26 is a M_r 110,000 surface glycoprotein with diverse functional properties, including having a potentially significant role in tumor development, and antibodies to CD26 mediate pleomorphic cellular functions. In this report, we show that binding of soluble anti-CD26 monoclonal Ab 1F7 inhibits the growth of the human CD30+ anaplastic large cell T-cell lymphoma cell line Karpas 299 in both in vitro and in vivo experiments. In vitro experiments show that 1F7 induces cell cycle arrest at the G₁-S checkpoint, associated with enhanced p21 expression that is dependent on de novo protein synthesis. Furthermore, experiments with a severe combined immunodeficient mouse tumor model demonstrate that 1F7 treatment significantly enhances survival of tumor-bearing mice by inhibiting tumor formation. Our data therefore suggest that anti-CD26 treatment may have potential clinical use for CD26+ hematological malignancies.

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