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(American Journal of Pathology. 1999;155:1353-1359.)
© 1999 American Society for Investigative Pathology

Animal Model

A Murine Xenograft Model for Human CD30+ Anaplastic Large Cell Lymphoma

Successful Growth Inhibition with an Anti-CD30 Antibody (HeFi-1)

Walther Pfeifer*, Edi Levi*, Tina Petrogiannis-Haliotis*, Leslie Lehmann{dagger}, Zhenxi Wang* and Marshall E. Kadin*

From the Department of Pathology,*
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; and the Department of Pediatric Oncology,{dagger}
Dana Farber Cancer Institute, Boston, Massachusetts

To develop a model for the biology and treatment of CD30+ anaplastic large cell lymphoma (ALCL), we transplanted leukemic tumor cells from a 22-month-old girl with multiple relapsed ALCL. Tumor cells were inoculated intraperitoneally into a 4-week-old SCID/bg mouse and produced a disseminated tumor within 8 weeks; this tumor was serially transplanted by subcutaneous injections to other mice. Morphology, immunohistochemistry, and molecular genetics which demonstrated the NPM-ALK fusion protein, resulting from the t(2;5)(p23;q35), confirmed the identity of the xenograft with the original tumor. The tumor produced transcripts for interleukin-1{alpha}, tumor necrosis factor-{alpha}, and interferon-{gamma} which could explain the patient's B-symptoms. Treatment of mice with monoclonal antibody (HeFi-1) which activates CD30 antigen administered on day 1 after tumor transplantation prevented tumor growth. Treatment with HeFi-1 after tumors had reached a 0.2 cm3 volume caused tumor growth arrest and prevention of tumor dissemination. We conclude that transplantation of CD30+ ALCL to SCID/bg mice may provide a valuable model for the study of the biology and design of treatment modalities for CD30+ ALCL.




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