Enhanced tumour specificity of an anti-carcinoembrionic antigen Fab' fragment by poly(ethylene glycol) (PEG) modification
| Autor: | Joan A. Boden, Derek Fisher, KA Chester, C Delgado, P. A. Keep, Angel Herráez, G. E. Francis, RB Pedley, R Boden, R. H. J. Begent |
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| Rok vydání: | 1996 |
| Předmět: |
Cancer Research
Poly ethylene glycol Antibodies Neoplasm Recombinant Fusion Proteins medicine.medical_treatment Biological Availability Mice Nude Polyethylene glycol Adenocarcinoma Polyethylene Glycols Immunoglobulin Fab Fragments Mice chemistry.chemical_compound Antigen Antibody Specificity PEG ratio medicine Animals Humans Tissue Distribution Sulfones biology Chemistry Peg modification Antibodies Monoclonal Molecular biology Carcinoembryonic Antigen Oncology Biochemistry Radioimmunotherapy Colonic Neoplasms Linear Models biology.protein PEGylation Female Binding Sites Antibody Antibody Neoplasm Transplantation Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.1996.32 |
| Popis: | Polyethylene glycol (PEG) modification of a chimeric Fab' fragment (F9) of A5B7 (alpha-CEA), using an improved coupling method, increases its specificity for subcutaneous LS174T tumours. PEGylation increased the area under the concentration-time curve (AUC0-144) in all tissues but there were significant differences (variance ratio test, F = 27.95, P < 0.001) between the proportional increases in AUC0-144, with the tumour showing the greatest increase. The increase in AUCtumour from F9 to PEG-F9 was similar to the reported increase from Fab' to F(ab')2 while the increase in AUCblood by PEGylation of F9 was only 21% of the reported increase from Fab' to whole IgG. A two sample t-test showed no significant differences between maximal tumour/tissue ratios for PEG-F9 and F9 while the tumour/tissue ratios for PEG-F9 remained high over a longer period, with tumour levels at least double those for F9. PEG-F9 emerges as a new generation antibody with potential advantages for both radioimmunotherapy and tumour imaging. Since there was a reduction in antigen binding, optimisation of PEGylation might further improve tumour specificity. The latter resulted from complex effects on both the entry into and exit rates from tumour and normal tissues in a tissue-specific fashion. |
| Databáze: | OpenAIRE |
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