Objective To investigate the anti-tumor effects in vitro and in vivo distribution of the human/murine chimeric antibody (D2C).Methods The CD71 positive target cells(K562,CEM and SMMC7721) and the effector cells ,fresh...Objective To investigate the anti-tumor effects in vitro and in vivo distribution of the human/murine chimeric antibody (D2C).Methods The CD71 positive target cells(K562,CEM and SMMC7721) and the effector cells ,freshly isolated human PBMC,with the ratio of target cells to effector cells 1:50,were incubated in various dilutions of D2C antibody(Ab).Antibody dependent cytotoxicity(AD-CC) was tested by using an LDH-release assay.Instead of effector cells,complement was added to the target cells (CEM,SMMC-7721) with various dilutions of D2C Ab.A method of counting death cells was used in complement dependent cytotoxicity(CDC) assay.Tumor localization and distribution of the chimeric antibody(D2C) were observed by labeling the chimeric Ab with radioiodine(^131I) and injecting in into nude mice(Balb/c nu/nu) transplanted with human hepatocellular carcinoma cells (SMMC-7721).Results A significant ADCC was observed with the increased concentration of the D2C Ab.Cytolysis of CD71-positive target cells by the D2C Ab was found in the presence of fresh rabbit complement.Labeled D2C administered by intraperitoneal as well as tumor regional in-jection,was visualized by SPECT. The distribution of D2C Ab in murine organs and tissues showed that non-specific binding was lower fol-lowing tumor regional administration than when the antibody was administered by an intraperitoneal injection.The human/murine chimeric antibody(D2C) has in vitro anti-tumor effects and can exert its effects in specific tumor localization.Its distribution and local effects in vi-vo can be detected by radioimmunoimaging. Conclusion CD71 human/murine chimeric antibody showed marked killing of tumor cells in vitro,and specific recognition and high affinity binding to tumor tissue in vivo.展开更多
The improved tumoricidal effect of the radioatibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic...The improved tumoricidal effect of the radioatibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal atibody (MAb) cocktail against human hepatocellular carcinoma. Therapeutic efficacy was determined by measuring the change in tumor size over a period, determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy. boioimmunotherapy of SMMC-7721 human hepatoma xenografts in athymic nude mice with combination of 131I labeled Hepama-1 and 131Llabeled 9403 mouse MAbs was more effective than using either Hepeam-1 or 9403 Mab alone The MAb cocktail could target a greater number of hepstoma cells and increase the magnitude of hepatoma cen uptde of radioamibodies. The in vjtro results explain the enhanced effect of the MAb cocktail in in vjvo model system.展开更多
To explore the inhibitory effects of anti-CD4 human/murine chimeric antibodies on lymphocyte proliferation, CD4^+ T cell apoptosis induced by anti-CD4 antibodies was examined. Annexin- V -FITC and PI double stain me...To explore the inhibitory effects of anti-CD4 human/murine chimeric antibodies on lymphocyte proliferation, CD4^+ T cell apoptosis induced by anti-CD4 antibodies was examined. Annexin- V -FITC and PI double stain method was employed to qualitatively and quantitatively determined CD4^+ T cell apoptosis induced by anti-CD4 antibodies. Our results showed that anti-CD4 chimeric antibodies could specifically induce CD4^+ T cell apoptosis. The ability of anti-CD4 chimeric antibodies to induce CD4^+ T cell apoptosis was related with the presence of monocytes. It is concluded that the further cross-linking of anti-CD4 antibodies is important for inducing CD4^+ T cell apoptosis.展开更多
基金National Sciences Foundation of China(No.39970693)
文摘Objective To investigate the anti-tumor effects in vitro and in vivo distribution of the human/murine chimeric antibody (D2C).Methods The CD71 positive target cells(K562,CEM and SMMC7721) and the effector cells ,freshly isolated human PBMC,with the ratio of target cells to effector cells 1:50,were incubated in various dilutions of D2C antibody(Ab).Antibody dependent cytotoxicity(AD-CC) was tested by using an LDH-release assay.Instead of effector cells,complement was added to the target cells (CEM,SMMC-7721) with various dilutions of D2C Ab.A method of counting death cells was used in complement dependent cytotoxicity(CDC) assay.Tumor localization and distribution of the chimeric antibody(D2C) were observed by labeling the chimeric Ab with radioiodine(^131I) and injecting in into nude mice(Balb/c nu/nu) transplanted with human hepatocellular carcinoma cells (SMMC-7721).Results A significant ADCC was observed with the increased concentration of the D2C Ab.Cytolysis of CD71-positive target cells by the D2C Ab was found in the presence of fresh rabbit complement.Labeled D2C administered by intraperitoneal as well as tumor regional in-jection,was visualized by SPECT. The distribution of D2C Ab in murine organs and tissues showed that non-specific binding was lower fol-lowing tumor regional administration than when the antibody was administered by an intraperitoneal injection.The human/murine chimeric antibody(D2C) has in vitro anti-tumor effects and can exert its effects in specific tumor localization.Its distribution and local effects in vi-vo can be detected by radioimmunoimaging. Conclusion CD71 human/murine chimeric antibody showed marked killing of tumor cells in vitro,and specific recognition and high affinity binding to tumor tissue in vivo.
文摘The improved tumoricidal effect of the radioatibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal atibody (MAb) cocktail against human hepatocellular carcinoma. Therapeutic efficacy was determined by measuring the change in tumor size over a period, determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy. boioimmunotherapy of SMMC-7721 human hepatoma xenografts in athymic nude mice with combination of 131I labeled Hepama-1 and 131Llabeled 9403 mouse MAbs was more effective than using either Hepeam-1 or 9403 Mab alone The MAb cocktail could target a greater number of hepstoma cells and increase the magnitude of hepatoma cen uptde of radioamibodies. The in vjtro results explain the enhanced effect of the MAb cocktail in in vjvo model system.
基金grant from the National Sciences Foundation of China (No. 39370628).
文摘To explore the inhibitory effects of anti-CD4 human/murine chimeric antibodies on lymphocyte proliferation, CD4^+ T cell apoptosis induced by anti-CD4 antibodies was examined. Annexin- V -FITC and PI double stain method was employed to qualitatively and quantitatively determined CD4^+ T cell apoptosis induced by anti-CD4 antibodies. Our results showed that anti-CD4 chimeric antibodies could specifically induce CD4^+ T cell apoptosis. The ability of anti-CD4 chimeric antibodies to induce CD4^+ T cell apoptosis was related with the presence of monocytes. It is concluded that the further cross-linking of anti-CD4 antibodies is important for inducing CD4^+ T cell apoptosis.
