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AssigneeBristol-Myers Company
InventorsPeter D. Senter, Mark G. Saulnier, Joseph P. Brown, David E. Kerr
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This invention relates to a novel method for the delivery of cytotoxic drugs to tumor cells by the administration of a tumor-specific antibody-enzyme conjugate that binds to the tumor cells, and the additional administration of a prodrug that is converted at the tumor site, in the presence of the antibody-bound enzyme, to an active cytotoxic drug. According to preferred embodiments of this invention, antibody-enzyme conjugates containing the enzyme, alkaline phosphatase ("AP"), have been used in conjunction with the novel prodrug, etoposide-4'-phosphate or 7-(2'-aminoethyl phosphate)mitomycin or a combination thereof, to effect killing of tumor cells. According to another embodiment of the invention, an antibody-enzyme conjugate containing the enzyme, penicillin V amidase ("PVA"), has been used in conjunction with a novel prodrug, N-(p-hydroxyphenoxyacetyl)adriamycin to effect killing of tumor cells. Still another embodiment of the invention relates to the use of an antibody-enzyme conjugate containing the enzyme, cytosine deaminase ("CD"), in combination with the prodrug, 5-fluorocytosine, to effect killing of tumor cells. The method, antibody-enzyme conjugates, prodrugs, pharmaceutical compositions and combinations of this invention provide for enhanced selective killing of tumor cells and are thus useful in the treatment of cancers and other tumors.
A method for the delivery of cytotoxic agents to tumor cells comprising:
A method for the delivery of a combination of cytotoxic agents to tumor cells comprising:
A method for the delivery of a combination of cytotoxic agents to tumor cells comprising:
The antibody-enzyme conjugate, L6-AP.
The antibody-enzyme conjugate, 96.5-AP.
The antibody-enzyme conjugate, 1F5-AP.
The antibody-enzyme conjugate, L6-PVA.
The antibody-enzyme conjugate, 1F5-PVA.
The antibody-enzyme conjugate, L6-CD.
The antibody-enzyme conjugate, 1F5-CD.
A compound having the formula:
A compound having the formula:
N-(p-hydroxyphenoxyacetyl)adriamycin.
N-(phenoxyacetyl)adriamycin.
A method for the delivery of cytotoxic agents to tumor cells comprising:
Dependencies are inferred from the claim text.