Cytotoxic drug conjugates and their delivery to tumor cells
First Claim
1. A therapeutic chemical conjugate including EGF as a first moiety, and a second moiety linked covalently to the EGF, said second moiety comprising a plurality of repeating units, each unit having the structure ##STR12## where L is selected from the group consisting of polyglutamic acid and polyaspartic acid, and T is selected from the group consisting of anthracycline drugs, bleomycin, melphalan, chlorambucil, cisplatin, adriamycin, daunomycin, and daunorubicin, and where said conjugate has a molecular weight of between 10,000 and 100,000 D and is effective in target cells in vivo and is internalized by tumor cells whereby the latter are inhibited or destroyed.
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Abstract
A therapeutic composition comprising a chemical conjugatge including a first moiety, other than an immunoglobulin or fragment thereof, such as epidermal growth factor, which preferentially binds to a tumor cell, and is internalized by the cell, and a second moiety linked to the first moiety, and comprising a biodegradable polymeric carrier, such as polyglutamic acid, to which one or more cytotoxic molecules, for instance, daunomycin, are attached. The degradation of the carrier by intracellular enzymes releases a cytotoxic agent, resulting in selective destruction of the tumor cells.
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Citations
10 Claims
- 1. A therapeutic chemical conjugate including EGF as a first moiety, and a second moiety linked covalently to the EGF, said second moiety comprising a plurality of repeating units, each unit having the structure ##STR12## where L is selected from the group consisting of polyglutamic acid and polyaspartic acid, and T is selected from the group consisting of anthracycline drugs, bleomycin, melphalan, chlorambucil, cisplatin, adriamycin, daunomycin, and daunorubicin, and where said conjugate has a molecular weight of between 10,000 and 100,000 D and is effective in target cells in vivo and is internalized by tumor cells whereby the latter are inhibited or destroyed.
Specification