[The specific photodynamic effect of monoclonal antibodies conjugated with hematoporphyrin derivative on gastric cancer in vitro and in vivo].
A murine monoclonal antibody (MoAb) BB4.3 raised against human gastric cancer cell line BGC823 was purified with Protein A-Sepharose CL-4B affinity chromatography and identified as IgG2a. The MoAb BB 4.3 was conjugated with hematoporphyrin derivative (HPD) by using carbodiimide. The conjugate HPD-BB4.3 retained both antibody activity and photochemical activity of HPD. In vitro the phototoxic effect of HPD-BB4.3 conjugate on target cells was about 15 times higher than that of free HPD. The target-selective photocytotoxicity of HPD-BB 4.3 was verified by the fact that this conjugate showed greater cytotoxicity than the corresponding normal mouse IgG (NIgG) conjugated with HPD, and that it showed less cytotoxicity to BB4.3 negative reaction cell line B-80 than to BGC 823; and moreover, its cytotoxicity to BGC823 cells could be blocked specifically by excess BB4.3 antibody. In an in vivo study, nude mice inoculated with 2 X 10(5) BGC823 cells were administered HPD-BB4.3, HPD, HPD-NIgG, HPD plus BB4.3 and PBS respectively; and were then exposed to light. Out of six animals treated with HPD-BB4.3 conjugate, four remained tumor-free for a long time. There was significant difference between HPD-BB 4.3 treated group and all control groups. The HPD-BB4.3 conjugate was also shown more than 40% inhibition of growth of established tumors in comparison with the control groups.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D017324:Hematoporphyrin Derivative; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D006415:Hematoporphyrins; D000922:Immunotoxins; D017324:Hematoporphyrin Derivative