A murine xenograft model for human CD30+ anaplastic large cell lymphoma. Successful growth inhibition with an anti-CD30 antibody (HeFi-1).

Abstract

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-1alpha, 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 cm(3) 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.

• Authors: W Pfeifer, E Levi, T Petrogiannis-Haliotis, L Lehmann, Z Wang, M E Kadin
• Journal: The American journal of pathology (Am J Pathol) Vol. 155 Issue 4 Pg. 1353-9 (Oct 1999) ISSN: 0002-9440 [Print] United States
• PMID: 10514417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Biomarkers, Tumor
• Ki-1 Antigen
• p80(NPM-ALK) protein
• Protein-Tyrosine Kinases

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Biomarkers, Tumor (biosynthesis)
• Cell Division (drug effects)
• Disease Models, Animal
• Female
• Flow Cytometry
• Gene Expression
• Humans
• Immunohistochemistry
• Immunophenotyping
• Infant
• Ki-1 Antigen (immunology, metabolism)
• Lymphoma, Large-Cell, Anaplastic (drug therapy, genetics, metabolism, pathology)
• Mice
• Mice, SCID
• Neoplasm Transplantation
• Protein-Tyrosine Kinases (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Transplantation, Heterologous