Single-Chain Antibodies in Pancreatic Cancer
| العنوان: | Single-Chain Antibodies in Pancreatic Cancer |
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| المؤلفون: | Surinder K. Batra, Barbara J.M. Booth, Gabriela Pavlinkova, Guy W. Beresford, David Colcher |
| المصدر: | Annals of the New York Academy of Sciences. 880:263-280 |
| بيانات النشر: | Wiley, 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Antibodies, Neoplasm, medicine.drug_class, medicine.medical_treatment, Molecular Sequence Data, Immunoglobulin Variable Region, Adenocarcinoma, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Epitope, Targeted therapy, History and Philosophy of Science, Antigen, Antigens, Neoplasm, In vivo, Pancreatic cancer, Biomarkers, Tumor, medicine, Animals, Humans, Amino Acid Sequence, Immunoglobulin Fragments, Glycoproteins, biology, Chemistry, General Neuroscience, Antibodies, Monoclonal, medicine.disease, Molecular biology, Recombinant Proteins, Pancreatic Neoplasms, biology.protein, Antibody, Single-Chain Antibodies |
| الوصف: | Pancreatic cancer is a therapeutic challenge for surgical and medical oncology. Development of specific molecular tracers for the diagnosis and treatment of this lethal cancer has been one of our major goals. Monoclonal antibodies (MAbs) have been successfully used as selective carriers for delivering radionuclides, toxins or cytotoxic drugs to malignant cell populations; therefore, monoclonal antibody technology has led to a significant amount of research into optimizing targeted therapy. This targeted therapy results in the selective concentration of cytotoxic agents or radionuclides in tumors and should lessen the toxicity to normal tissues, which would normally limit the dosage and effectiveness of systemically administered drugs. The MAb CC49 reacts with a unique disaccharide, Sialyl-Tn, present on tumor-associated mucin (TAG-72) expressed by a majority of human adenocarcinomas. The unique Sialyl-Tn epitope has provided a potential target for immunotherapy of cancer. A single chain Fv (scFv) recombinant protein from CC49 MAb was prepared by engineering the DNA fragments for coding heavy-chain and light-chain variable regions with an appropriate oligonucleotide linker. scFv molecules, when compared to intact MAbs and the more conventional enzymatically derived F(ab')2 and Fab' fragments, offer several advantages as carriers for the selective delivery of radionuclides to tumors. The divalent antibody fragments (sc(Fv)2 or (scFv)2) display an affinity constant similar to that of the intact CC49 IgG and are stable with storage, and after radiolabeling. In preclinical studies, both the covalent and the non-covalent dimeric scFvs exhibit excellent tumor targeting properties with characteristics similar to those of the monomer, e.g., the rapid blood clearance, low kidney uptake and small size suitable for rapid penetration through tumor tissue. Increased tumor targeting of the dimers are probably due to their increased functional affinity attributable to valency, coupled with their higher molecular weight and fewer interactions with normal organs. These properties make these constructs superior to monovalent CC49 scFv. The relatively high tumor uptake, the in vitro and in vivo targeting specificity, and the stability in storage demonstrated by the dimeric CC49 sc(Fv)2 makes it a promising delivery vehicle for therapeutic applications in pancreatic cancer. |
| تدمد: | 1749-6632 0077-8923 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64b9a8d31ee3b421573f5278a7fb73dc https://doi.org/10.1111/j.1749-6632.1999.tb09531.x |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....64b9a8d31ee3b421573f5278a7fb73dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17496632 00778923 |
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