| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Immunoscintigraphy has been exclusively studied, since many monoclonal antibodies associated with tumors have been developed. Many factors are involved in the accumulation of antibody into the tumors; Especially characteristics of tumors, such as their vascularity, the antigen level, sites to produce antigens, and presence of necrosis, affect the localization of injected antibody. In other words, biodistributions of injected antibodies reflect the variabilities and specificities of tumors. Standing at this point, we have intended to clarify biochemical and immunological properties of tumor through immunoscintigraphies of several kinds of tumors. We also reviewed radioimmunodetection: its problems and future. In these reviews, we have pointed out factors which influenced the localization of antibodies into tumors. Two factors have been picked up here. One is the effect of circulating an tigen and the other is that of antigen expression. Using tumor models which consisted of the human he
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patocellular carcinoma, NuE and PLC cell lines producing AFP xenografted in nude mice, and I-125-labeled monoclonal antibody 19FI2 raised against AFP, following results were obtained.
(1) Endogeneous circulating antigen retained the antibody in the whole body for a longer period. The ability of monoclonal antibodies to target tumors was influenced not only by how much antigen was present but also how rapid antigen was cleared in the blood. (2) Treatment of NuE with interferon (IFN) alphaA increased the surface expression of AFP in an IFN-alphaA dose dependent manner. The IFN-alphaA treatment substantially increased the localization of labeled 19FI2 to the NuE grown in athmic mice.
It could be said that adequate tumors and monoclonal antibodies for immunoscintigraphy were tumors which excreate few antigen endogeneously, and antibodies that recognize antigen present in the surface of tumor cells. Co- administration of biological response modifiers, such as interferon, together with antibody is very promising not only since they would change the biodistribution but also since they might reduce the side effects caused by the injection of antibody. Less
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