Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model.
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-2IT-BAT-Lym-1 therapy induced a response rate (complete and partial responses) of approximately 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.
Kroger
L A
LA
Molecular Cancer Institute, Sacramento, California 95816, USA.
DeNardo
S J
SJ
DeNardo
G L
GL
Xiong
C Y
CY
Winthrop
M D
MD
Gumerlock
P H
PH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003301:Copper Radioisotopes / Q000627:therapeutic use*; D019254:Genes, bcl-2; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008223:Lymphoma / Q000532:radiotherapy*; D051379:Mice; D009368:Neoplasm Transplantation; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016499:Radioimmunotherapy; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; D006684:HLA-DR Antigens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2