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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-11-3601.
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Blood, 1 July 2003, Vol. 102, No. 1, pp. 284-288
NEOPLASIA
Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507
Zhuo Zhang,
Meili Zhang,
Jeffrey V. Ravetch,
Carolyn Goldman, and
Thomas A. Waldmann
From the Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; and the Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY.
Adult T-cell leukemia (ATL) develops in a small proportion of individuals infected with the retrovirus human T-cell leukemia virus (HTLV-1). We evaluated the efficacy of MEDI-507 (a humanized monoclonal antibody directed against CD2) alone and in combination with humanized anti-Tac (HAT) directed toward CD25, the interleukin-2 receptor  (IL-2R) using a human adult T-cell leukemia xenograft model. Weekly treatments (4) with HAT significantly prolonged the survival of the ATL-bearing mice when compared with phosphate-buffered saline (PBS)–treated controls (P < .0001). Mice treated with MEDI-507 (100 µg/wk for 4 weeks) survived longer than those treated with HAT (P < .0025). Furthermore, prolonged treatment (6 months) of ATL with MEDI-507 significantly improved the outcome when compared with a short course (4 weeks) of therapy (P < .0036). Such treatment with weekly MEDI-507 for 6 months led to a prolonged survival of the ATL-bearing mice that was comparable with the survival observed in the control group of mice that did not receive a tumor or therapeutic agent. We also found that the expression of Fc receptors (FcR) on polymorphonuclear leukocytes and monocytes was required for MEDI-507–mediated tumor killing in vivo. Thus, the tumor-killing mechanism with MEDI-507 in vivo required the expression of the receptor FcRIII on polymorphonuclear leukocytes and monocytes, suggesting that it is mediated by a form of antibody-dependent cellular cytotoxicity. These results demonstrate that MEDI-507 has therapeutic efficacy on ATL in vivo and provides support for a clinical trial involving this monoclonal antibody in the treatment of patients with CD2-expressing leukemias and lymphomas. (Blood. 2003; 102:284-288)
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