Mutagenized IL 13-based chimeric molecules
AssigneeThe Penn State Research Foundation
InventorWaldemar Debinski
Life of this patent
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Abstract
This invention provides mutagenized interleukin 13 molecules that show improved specificity for the restricted (IL4 independent) IL13 receptor and reduced cross-reactivity with the IL4/IL4 shared receptor. The mutagenized IL13 molecules include one or more mutations in a domain that interacts with the 140 kDa hIL4Rβ or the hIL13Rα1 subunit. These mutagenized IL13 molecules provide effective targeting moieties in chimeric molecules (e.g. fusion proteins) that specifically deliver effector molecules (e.g. cytotoxins) to cells overexpressing IL13 receptors (e.g. cancer cells such as gliomas).
Claims12
A chimeric molecule having the formula:
- R1—(L)j—(R2)n
- wherein R1 is a polypeptide comprising the amino acid sequence of SEQ ID NO:5;
- j is 0 or 1;
- n is at least 1;
- R2 is a cytotoxin;
- and
- L is a linker.
A method of delivering an effector molecule to a cell bearing an interleukin 13 receptor (IL13R), said method comprising the step of contacting said cell with a chimeric molecule comprising said effector molecule attached to a polypeptide comprising the amino acid sequence of SEQ ID NO:5.
A method of inhibiting the growth of a cell expressing an IL13 receptor (IL13R), said method comprising contacting said cell with a cytotoxic molecule comprising a cytotoxin covalently attached to a polypeptide comprising the amino acid sequence of SEQ ID NO:5.
A pharmaceutical composition comprising
- a pharmacologically acceptable excipient;
- and
- a cytotoxic molecule comprising a cytotoxin covalently attached to a polypeptide comprising the amino acid sequence of SEQ ID NO:5.
Dependencies are inferred from the claim text.