Cleavable Linkers to Enhance Selectivity of Antibody-Targeted Therapy of Cancer
| Autor: | David L. Kukis, Ilse Novak-Hofer, Sally J. DeNardo |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Immunoconjugates Metabolic Clearance Rate medicine.drug_class medicine.medical_treatment Kidney Monoclonal antibody Targeted therapy Neoplasms medicine Animals Humans Radiology Nuclear Medicine and imaging Pharmacology biology Chemistry Cancer Kidney metabolism General Medicine Immunotherapy Radioimmunotherapy medicine.disease Cross-Linking Reagents Liver Oncology Biochemistry biology.protein Radiopharmaceuticals Antibody Linker |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 16:457-467 |
| ISSN: | 1557-8852 1084-9785 |
| Popis: | Radioimmunotherapy of cancer utilizes anti-tumor antibodies or antibody fragments conjugated to radionuclides to deliver radiation selectively to tumors. However, radiolabeled proteins deposit radioactivity in normal organs that metabolize or conserve proteins and peptides, primarily liver and kidneys. To accelerate the clearance of radioactivity from normal tissues, linkers between the antibody or antibody fragment and the radioactive moiety have been designed for cleavage in the liver and kidneys, to liberate low molecular weight radioactive species for rapid excretion. Modest success in improving the tumor-to-liver and tumor-to-kidney radiation dose ratios have been achieved in preclinical studies. Such changes when taken to clinical studies have suggested useful impact on therapeutic work. Recent advances in the development of cleavable linkers are described. |
| Databáze: | OpenAIRE |
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