Molecular Biological Approach towards Efficient Radioimmunotherapy

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The aim of this study is to evaluate the tumor cells treated with radiolabeled monoclonal antibodies from the molecular biological point of view. The effects of dose of radiolabeled antibodies and fractionation were investigated to get the following results.1. Human gastric cancer cells producing CEA were incubated with I-131-labeled anti-CEA monoclonal antibody :(1) No apoptosis was observed in tumor cells.(2) Cytotoxicity was dose dependent, and repeated incubation caused higher toxicity than one incubations.2. Murine leukemia cells were incubated with I-131-labeled monoclonal antibody which was reactive with cell surface antigen :(1) Apoptosis was observed in tumor cells.(2) Apoptosis was observed in tumor cells which were incubated with I-131-labeled irrelevant antibody or I-131 ; indicating that apoptosis is not specific for radiolabeled antibodies.3. Athymic nude mice bearing human gastric cancer xenografts were injected with I-131-labeled anti-CEA monoclonal antibody :(1) No apoptosis was observed in tumor cells by any dose of I-131-labeled antibody.(2) Necrosis was observed in xenografts when mice were injected with I-131-labeled antibody intratumorally. Fractionation reduced the uptake of I-131 in the tumors.4. Hetero, athymic nude, or SCID mice bearing leukemia cells intraperitoneally were injected with I-131-labeled antibody :(1) Apoptosis was observed in leukemia cells in any mice.(2) Apoptosis was observed in only hetero mice by the low dose of I-131-antibody. High does of I-131-labeled antibody caused the radiation damage in SCID mice ; indicating that apoptosis occurred through the immunogenic pathways.5.The study suggested that :(1) Apoptosis would not be mainly involved in solid tumors by radioimmunotherapy.(2) Apoptosis is an important factors in hematological tumors in conjunction with the immunogenecity from the host when it is treated by radioimmunotherapy.