Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model

Linda A. Kroger, Sally J. DeNardo, Gerald L Denardo, Cheng Yi Xiong, Michelle D. Winthrop, Paul H. Gumerlock

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Radioimmunotherapy using monoclonal antibodies against tumor-associated antigens has been particularly promising in the treatment of radiosensitive malignancies such as lymphoma. 67Cu has excellent physical and biochemical properties for radioimmunotherapy. 67Cu-2IT-BAT-Lym-1 has been used in preclinical and clinical trials, where an exceptionally long residence time of 67Cu on tumor was observed. BCL-2, a proto-oncogene that promotes cell survival by blocking apoptotic cell death, is overexpressed in most B-cell lymphomas including Raji human Burkitt's lymphoma cells. In this study, therapeutic efficacy and BCL-2 gene and protein expression levels were examined in Raji xenografts in mice after 67Cu-2IT-BAT-Lym-1 radioimmunotherapy. 67Cu-2ITBAT-Lym-1 therapy induced a response rate (complete and partial responses) of ~50%. BCL-2 gene expression was decreased 3 h after radioimmunotherapy, followed by a decrease in Bcl-2 protein by 24 h. Decreases in BCL-2 gene and protein expression preceding observations of 67Cu-2IT-BAT-Lym-1 therapeutic effect suggest that down- regulation of BCL-2 leaves cells more likely to be killed by low dose-rate radiation from radioimmunotherapy.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume5
Issue number10 SUPPL.
StatePublished - Oct 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model'. Together they form a unique fingerprint.

  • Cite this

    Kroger, L. A., DeNardo, S. J., Denardo, G. L., Xiong, C. Y., Winthrop, M. D., & Gumerlock, P. H. (1999). Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model. Clinical Cancer Research, 5(10 SUPPL.).