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 Citations (Scopus)

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

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Radioimmunotherapy
Lymphoma
Gene Expression
Proteins
Therapeutics
Burkitt Lymphoma
Proto-Oncogenes
B-Cell Lymphoma
Neoplasm Antigens
Therapeutic Uses
Heterografts
Neoplasms
Cell Survival
Cell Death
Down-Regulation
Monoclonal Antibodies
copper-67-2IT-BAT-Lym-1
Clinical Trials
Radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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.).

Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model. / Kroger, Linda A.; DeNardo, Sally J.; Denardo, Gerald L; Xiong, Cheng Yi; Winthrop, Michelle D.; Gumerlock, Paul H.

In: Clinical Cancer Research, Vol. 5, No. 10 SUPPL., 10.1999.

Research output: Contribution to journalArticle

Kroger, LA, DeNardo, SJ, Denardo, GL, Xiong, CY, Winthrop, MD & Gumerlock, PH 1999, 'Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model', Clinical Cancer Research, vol. 5, no. 10 SUPPL..
Kroger, Linda A. ; DeNardo, Sally J. ; Denardo, Gerald L ; Xiong, Cheng Yi ; Winthrop, Michelle D. ; Gumerlock, Paul H. / Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 10 SUPPL.
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