Enhancement of colorectal tumor targeting using a novel biparatopic monoclonal antibody against carcinoembryonic antigen in experimental radioimmunoguided surgery
| Autor: | Jin S. Ryu, Hyun K. Hong, Ho J. Kim, Jin C. Kim, Seung Jun Oh, Seon Ae Roh, Kum H. Koo, Walter F. Bodmer, Jang H. Ryu |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty medicine.drug_class Transplantation Heterologous Mice Nude Adenocarcinoma Monoclonal antibody Sensitivity and Specificity Epitope Immunoglobulin G Iodine Radioisotopes Epitopes Immunoglobulin Fab Fragments Mice Carcinoembryonic antigen Antibody Specificity Biomarkers Tumor Tumor Cells Cultured medicine Animals Tissue Distribution Avidity Radioimmunoguided surgery Radiometry biology business.industry Antibodies Monoclonal Technetium medicine.disease Carcinoembryonic Antigen Neoplasm Proteins Protein Structure Tertiary Radioimmunodetection Surgery Computer-Assisted Oncology Cancer research biology.protein Colorectal Neoplasms Clone (B-cell biology) business Neoplasm Transplantation |
| Zdroj: | International Journal of Cancer. 97:542-547 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.1630 |
| Popis: | Biparatopic CEA, carcinoembryonic antigen (MAb) was newly designed and tested as to whether it enhanced the accuracy of tumor detection by reducing non-specific binding in experimental radioimmunoguided surgery. Biparatopic MAb was prepared by using cross-linking of reduced Fab' fragments from PR1A3 and T84.66. Fifty-nine tumors from 2 human colorectal carcinoma cell lines with high (KM-12c) and low (Clone A) carcinoembryonic antigen (CEA) expression were successfully implanted subcutaneously on the backs of 42 nude mice. Tumors were localized using 125I-labeled MAbs: IgG, F(ab')(2) and Fab' of PR1A3, and biparatopic MAb of PR1A3 and T84.66. Radioactivity counted on a portable radioisotope detector correlated well with that counted on a gamma counter (p < 0.001). Accumulations of radioactivity in control mice without tumorigenesis were the greatest in PR1A3 IgG-pretreated mice and the least in biparatopic MAb-pretreated mice. Tumors of 2 cell lines did not differ in the distribution of radiolabeled MAbs. Localization indices of the tumor in various organs revealed 1.3 to 4.1 in PR1A3 IgG-pretreated mice, 2.4 to 6.6 in fragment MAbs of PR1A3-pretreated mice and 2 to 4.6 in biparatopic MAb-pretreated mice. Silver grains and immune staining were predominantly distributed in tumor cells of all types of MAb-pretreated mice. Sensitivity and specificity of tumor localization by radioimmunoguided surgery (RIGS) were the highest in the biparatopic MAb-pretreated mice (90.9% and 94.5%, respectively) and the least in the PR1A3 IgG-pretreated mice (50% and 72%). The biparatopic MAb using 2 anti-CEA MAbs against different epitopes achieved a great affinity and avidity with accurate localization of colorectal carcinoma in experimental radioimmunoguided surgery. |
| Databáze: | OpenAIRE |
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