Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen.

Kamigaki,T; Ajiki,T; Yamamoto,M; Kuroda,Y

doi:10.3892/ijo.14.1.139

Jan 1999 Volume 14 Issue 1

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Jan 1999 Volume 14 Issue 1

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Article

Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen.

Authors:
- T Kamigaki
- T Ajiki
- M Yamamoto
- Y Kuroda
View Affiliations / Copyright

Affiliations: First Department of Surgery, Kobe University School of Medicine, Chuo-ku, Kobe 650-0017, Japan.
Pages: 139-183
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Published online on: January 1, 1999

https://doi.org/10.3892/ijo.14.1.139
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Abstract

We investigated the effect of stabilized Fab oligomerization by disuccinimidyl suberate on tumor uptake in a pancreatic carcinoma xenograft model in nude mice. Recombinant mouse/human chimeric Fab of the anti-carcinoembryonic antigen (CEA) monoclonal antibody A10, which was previously shown to react specifically with gastrointestinal cancers was used in this study. Fab homo-oligomers (dimers and trimers) chemically linked with ethylene bonds (C-C oligomers) were produced by linkage of chimeric Fab. Oligomers with C-C bonds had similar immunoreactivity against human CEA to parental Fab monomer. In biodistribution studies in animals bearing pancreatic carcinoma xenografts, at 12 and 24 h after infusion, C-C oligomers showed significantly greater uptakes in tumors than Fab or F(ab')2 but lower than IgG. However, oligomers with C-C bonds maintained higher tumor to normal tissue specificity ratios than IgG 24 h post-infusion. In conclusion, tumor uptake was enhanced by Fab oligomerization with C-C bonds, compared to Fab or F(ab')2, perhaps due to the larger molecular size. It was also shown that C-C Fab oligomers could have a potency to deliver high-dose radionuclides with reduced radio-uptakes in normal tissues for the radioimmunotherapy of gastrointestinal carcinomas.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen.

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Abstract

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