The use of antifibrin antibodies for the destruction of tumor cells

Lee, F. H.; Berczi, István; Fujimoto, Shigeyoshi; Sehon, A.H.

doi:10.1007/bf00199629

Cited by 11 publications

References 10 publications

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Preparation of four daunomycin‐monoclonal antibody 79IT/36 conjugates with anti‐tumour activity

Gallego

Price

Baldwin

1984

Intl Journal of Cancer

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As an approach to developing more specific anti-tumour therapeutic agents, daunomycin has been covalently linked to the human tumour localizing, murine monoclonal antibody 791T/36. Four procedures for coupling drug to antibody were investigated. The sugar amino group of daunomycin was modified by reaction with succinic anhydride or cis aconitic anhydride and these derivatives were linked to antibody, a carbodiimide reagent being used to produce stable peptide bonding. Alternatively, 14-bromo daunomycin was linked directly to antibody or antibody containing free thiol groups introduced by means of the heterobifunctional reagent SPDP [N-succinimidyl-3 (2-pyridyldithio) propionate] thus producing a thioether linkage. Each of the conjugates, with drug-antibody ratios of 3 to 4:1, retained a proportion of drug activity although the succinic anhydride derivative was the least cytotoxic. The three other conjugates specifically bound to tumour cells expressing the 791T/36 antibody defined antigen. In short-term assays in which tumour cells were briefly exposed to conjugates and then washed to remove non-bound conjugate, it was determined that the conjugate with the cis aconityl linkage displayed the greatest selective cytotoxicity against tumour cells reactive with the 791T/36 antibody. These studies illustrate the feasibility of preparing chemically defined drug-antibody conjugates retaining cytotoxicity and selectivity of action against tumour cells.

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