Systemic toxicity of drugs is one of the most serious problems in cancer chemotherapy and frequently is dose limiting. Specific delivery of cytotoxic drugs to cancer cells remains among the most intractable problems of cancer therapy. Targeted delivery of anti-proliferation drugs through the cell surface receptors that are over expressed on cancer cells can reduce systemic toxicity and increase effectiveness of a treatment.
The present invention describes cytotoxic compounds with an intracellular target that can selectively enter tumor cells through specific receptors on the cell surface. The invention also describes a conjugate comprising a cytotoxic agent, a linker arm and a ligand capable of delivering a cytotoxic agent in a cell specific manner. Such conjugates of a cytotoxic agent and a ligand (delivery moiety) have increased selectivity for tumor cells. The toxic moiety and the ligand are joined by a linker arm that is stable in circulation, but is easily cleaved in lysosomes upon internalization of the conjugate. A panel of compounds comprised of a variety of cytotoxic warheads, against various intracellular targets linked to an assortment of ligands, has been developed and tested in a model system. Ligand moieties of these conjugates are capable of specific delivery of cytotoxic agents to receptors that are frequently over expressed in gastric, colon, lung, breast, ovarian and pancreatic tumors. These compounds have the potential to be highly effective anti-tumor agents with considerably little negative effect. This disclosed technology could provide new and exciting methodologies to treat cancer.
Anti-tumor agent for gastric, colon, lung, breast, ovarian and pancreatic tumors.
U.S. Patent Application No. 10/505,239 filed 19 Aug 2004, claiming priority to 27 Feb 2002 (HHS Reference No. E-057-2002/2-US-02)
Nadya I. Tarasova et al. (NCI)
Available for licensing.
Collaborative Research Opportunity:
The National Cancer Institute Structural Biophysics Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Conjugates of Ligand, Linker, and Cytotoxic Agent and Related Compositions and Methods of Use. Please contact John D. Hewes, Ph.D. at 301-435-3121 or email@example.com for more information.
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