Monoclonal antibodies （MAbs） are a relatively new innovation in cancer treatment. At present, some monoclonal antibodies have increased the efficacy of the treatment of certain tumors with acceptable safety profiles...Monoclonal antibodies （MAbs） are a relatively new innovation in cancer treatment. At present, some monoclonal antibodies have increased the efficacy of the treatment of certain tumors with acceptable safety profiles. When monoclonal antibodies enter the body and attach to cancer cells, they function in several different ways： first, they can trigger the immune system to attack and kill that cancer cell; second, they can block the growth signals; third, they can prevent the formation of new blood vessels. Some naked MAbs such as rituximab can be directed to attach to the surface of cancer cells and make them easier for the immune system to find and destroy. The ability to produce antibodies with limited immunogeni-city has led to the production and testing of a host of agents, several of which have demonstrated clinically important antitumor activity and have received U.S. Food ＆ Drug Administration （FDA） approval as cancer treatments. To reduce the immunogenicity of murine anti- bodies, murine molecules are engineered to remove the immuno- genic content and to increase their immunologic efficiency. Radiolabeled antibodies composed of antibodies conjugated to radionuclides show efficacy in non-Hodgkin＇s lymphoma. Anti-vascular endothelial growth factor （VEGF） antibodies such as bevacizumab intercept the VEGF signal of tumors, thereby stopping them from connecting with their targets and blocking tumor growth. Trifunctional antibodies have revealed a new perspective in cancer therapy extending beyond primary destruction of tumor cells.展开更多
AIM: To investigate the inhibitory efficacy of <sup>125</sup>I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC).METHODS: bFGF mAb was prepared ...AIM: To investigate the inhibitory efficacy of <sup>125</sup>I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC).METHODS: bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with <sup>125</sup>I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of <sup>125</sup>I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), <sup>125</sup>I-bFGF mAb, <sup>125</sup>I plus bFGF mAb, bFGF mAb, or <sup>125</sup>I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction.RESULTS: The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 °C. After coupling, <sup>125</sup>I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 °C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, <sup>125</sup>I, bFGF mAb, <sup>125</sup>I plus bFGF mAb, and <sup>125</sup>I-bFGF mAb groups was 1.88 ± 0.25, 1.625 ± 0.21, 1.5 ± 0.18, 1.41 ± 0.16, and 0.98 ± 0.11 g, respectively. The tumor inhibition ratio in the <sup>125</sup>I, bFGF mAb, <sup>125</sup>I plus bFGF mAb, and <sup>125</sup>I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the <sup>125</sup>I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the <sup>125</sup>I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for <sup>125</sup>I group) compared with the control group.CONCLUSION: <sup>125</sup>I-bFGF mAb inhibits growth of HCC xenografts. The coupling effect of <sup>125</sup>I-bFGF mAb is more effective than the concomitant use of <sup>125</sup>I and bFGF mAb.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （Grant nos. 30800561 and 31171303） and Tianjin Natural Science Foundation （Grant no. 09JCZDJC18100）.
文摘Monoclonal antibodies （MAbs） are a relatively new innovation in cancer treatment. At present, some monoclonal antibodies have increased the efficacy of the treatment of certain tumors with acceptable safety profiles. When monoclonal antibodies enter the body and attach to cancer cells, they function in several different ways： first, they can trigger the immune system to attack and kill that cancer cell; second, they can block the growth signals; third, they can prevent the formation of new blood vessels. Some naked MAbs such as rituximab can be directed to attach to the surface of cancer cells and make them easier for the immune system to find and destroy. The ability to produce antibodies with limited immunogeni-city has led to the production and testing of a host of agents, several of which have demonstrated clinically important antitumor activity and have received U.S. Food ＆ Drug Administration （FDA） approval as cancer treatments. To reduce the immunogenicity of murine anti- bodies, murine molecules are engineered to remove the immuno- genic content and to increase their immunologic efficiency. Radiolabeled antibodies composed of antibodies conjugated to radionuclides show efficacy in non-Hodgkin＇s lymphoma. Anti-vascular endothelial growth factor （VEGF） antibodies such as bevacizumab intercept the VEGF signal of tumors, thereby stopping them from connecting with their targets and blocking tumor growth. Trifunctional antibodies have revealed a new perspective in cancer therapy extending beyond primary destruction of tumor cells.
基金Supported by the National Natural Science Foundation of China,No.81273814Guangdong Province Key Scientific Research Grant,No.2013A022100031
文摘AIM: To investigate the inhibitory efficacy of <sup>125</sup>I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC).METHODS: bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with <sup>125</sup>I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of <sup>125</sup>I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), <sup>125</sup>I-bFGF mAb, <sup>125</sup>I plus bFGF mAb, bFGF mAb, or <sup>125</sup>I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction.RESULTS: The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 °C. After coupling, <sup>125</sup>I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 °C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, <sup>125</sup>I, bFGF mAb, <sup>125</sup>I plus bFGF mAb, and <sup>125</sup>I-bFGF mAb groups was 1.88 ± 0.25, 1.625 ± 0.21, 1.5 ± 0.18, 1.41 ± 0.16, and 0.98 ± 0.11 g, respectively. The tumor inhibition ratio in the <sup>125</sup>I, bFGF mAb, <sup>125</sup>I plus bFGF mAb, and <sup>125</sup>I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the <sup>125</sup>I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the <sup>125</sup>I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for <sup>125</sup>I group) compared with the control group.CONCLUSION: <sup>125</sup>I-bFGF mAb inhibits growth of HCC xenografts. The coupling effect of <sup>125</sup>I-bFGF mAb is more effective than the concomitant use of <sup>125</sup>I and bFGF mAb.
