Carbohydrate-derivatized immunoconjugate of the anti-(carcinoembryonic antigen) monoclonal antibody C46: immunohistological reactivity and pharmacokinetic comparison with a randomly derivatized C46 immunoconjugate
| Autor: | C J D'Aleo, Steven C. Gilman, Rosenstraus Mj, Davis Wl, Lopes Ad |
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| Rok vydání: | 1990 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty medicine.drug_class Immunology Carbohydrates Dose-Response Relationship Immunologic Mice Nude Immunofluorescence Monoclonal antibody Mice Carcinoembryonic antigen Antigen Antibody Specificity Neoplasms medicine Immunology and Allergy Animals Humans Tissue Distribution biology medicine.diagnostic_test Chemistry Antibodies Monoclonal Pentetic Acid medicine.disease Immune complex Immunoconjugate Carcinoembryonic Antigen Oncology biology.protein Cancer research Adenocarcinoma Antibody Neoplasm Transplantation Granulocytes |
| Zdroj: | Cancer immunology, immunotherapy : CII. 32(4) |
| ISSN: | 0340-7004 |
| Popis: | In this study, a site-specific glycyl-tyrosyl-(N-epsilon-diethylenetriaminepentaacetic acid)-lysine (GYK-DTPA) immunoconjugate of the anti-carcinoembryonic antigen monoclonal antibody C46 (C46-GYK-DTPA) was characterized by immunohistological and immunofluorescence methods for reactivity with normal and neoplastic human tissues. In addition, pharmacokinetic studies assessed the ability of C46-GYK-DTPA labeled with 111In to localize to and image human tumor xenografts in nude mice. The native antibody and the site-specific immunoconjugate exhibited similar patterns of reactivity with normal human tissues. C46 did not bind to the surface of normal human granulocytes, which indicates lack of reactivity with normal cross-reacting antigen. C46-GYK-DTPA reacted with 100% of the colon, breast and renal carcinomas examined and with two of three lung carcinomas, but did not react with any sarcomas, melanomas or lymphomas examined. Intravenously administered C46-GYK-DTPA-111In rapidly localized to and imaged LS174T human colon adenocarcinoma xenografts in nude mice, reaching maximal levels of about 25% of injected dose/g tumor within 1 day. No unusual localization to any non-tumor tissue or organ was seen; the level of radioactivity in the normal tissues and organs was at or below that in the blood. The accessible binding sites in 1 g tumors appeared to be saturated at an antibody dose between 100 micrograms and 1000 micrograms/mouse. Further, in a direct in vivo comparison, the site-specific conjugate C46-GYK-DTPA had more favorable pharmacokinetics and better tumor localization than a randomly derivatized C46 immunoconjugate (C46-DTPA). These findings suggest that the site-specific immunoconjugate C46-GYK-DTPA may be useful in the diagnosis and therapy of colon cancer and other adenocarcinomas expressing carcinoembryonic antigen. |
| Databáze: | OpenAIRE |
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