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 language | English (US) |
|---|---|
| Journal | Clinical Cancer Research |
| Volume | 5 |
| Issue number | 10 SUPPL. |
| State | Published - Oct 1999 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model
AU - Kroger, Linda A.
AU - DeNardo, Sally J.
AU - Denardo, Gerald L
AU - Xiong, Cheng Yi
AU - Winthrop, Michelle D.
AU - Gumerlock, Paul H.
PY - 1999/10
Y1 - 1999/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032589758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032589758&partnerID=8YFLogxK
M3 - Article
C2 - 10541336
AN - SCOPUS:0032589758
VL - 5
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 10 SUPPL.
ER -