An improved synthesis of a methotrexate-albumin-791T/36 monoclonal antibody conjugate cytotoxic to human osteogenic sarcoma cell lines.
কীওয়ার্ডস
বিমূর্ত
Improvements have been made in the synthesis of a drug-carrier-antibody conjugate using methotrexate as the drug, human serum albumin as the carrier, and a monoclonal antibody against a human osteogenic sarcoma cell line (791T/36). The improvements have resulted in a higher and more reproducible substitution of serum albumin by methotrexate, and improvements in the coupling of methotrexate covalently linked to human serum albumin to antibody resulting in a greater ease and efficiency of conjugation. The improvements have led to a conjugate of increased cytotoxicity while retaining the previously reported specificity. A conjugate is reported which shows cytotoxicity of 1.1 ng/ml (2.4 nM) with respect to methotrexate and 6 X 10(-11) M with respect to antibody in a clonogenic assay on 791T cells. This cytotoxicity is greater than that obtained using free methotrexate (2.8 ng/ml; 6.1 nM) and implies that drug cytotoxicity can be considered as the sum of drug uptake and the number of drug molecules required to kill a cell. This further suggests that antibodies could provide a potent delivery system for drugs which are poorly taken up by cells.