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US 2011/0212162 A1Published application
Lymphatic zip codes in tumors and pre-malignant lesions
AssigneesSanford-Burnham Medical Research Institute, The Regents of the University of California
InventorsErkki Ruoslahti, Lianglin Zhang, Douglas Hanahan
Life of this patent
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Abstract
Disclosed herein are compositions and methods for and involving selectively targeting tumor lymphatics.
Claims29
An isolated peptide having a length of up to 50 amino acids comprising
- (a) CASLSCR (SEQ ID NO:10), CASLSCR (SEQ ID NO:10) with one, two or three conservative amino acid substitutions, CASLSCR (SEQ ID NO:10) with one or two non-conservative amino acid substitution, or CASLSCR (SEQ ID NO:10) with one or two non-conservative amino acid substitution and one, two or three conservative amino acid substitutions;
- (b) CLDGGRPKC (SEQ ID NO:5), CLDGGRPKC (SEQ ID NO:5) with one, two, three or four conservative amino acid substitutions, CLDGGRPKC (SEQ ID NO:5) with one, two or three non-conservative amino acid substitution, or CLDGGRPKC (SEQ ID NO:5) with one, two or three non-conservative amino acid substitution and one, two, three or four conservative amino acid substitutions;
- (c) CREAGRKAC (SEQ ID NO:6), CREAGRKAC (SEQ ID NO:6) with one, two, three or four conservative amino acid substitutions, CREAGRKAC (SEQ ID NO:6) with one, two or three non-conservative amino acid substitution, or CREAGRKAC (SEQ ID NO:6) with one, two or three non-conservative amino acid substitution and one, two, three or four conservative amino acid substitutions;
- (d) CSMSAKKKC (SEQ ID NO:7), CSMSAKKKC (SEQ ID NO:7) with one, two, three or four conservative amino acid substitutions, CSMSAKKKC (SEQ ID NO:7) with one, two or three non-conservative amino acid substitution, or CSMSAKKKC (SEQ ID NO:7) with one, two or three non-conservative amino acid substitution and one, two, three or four conservative amino acid substitutions;
- (e) CKTRVSCGV (SEQ ID NO:8), CKTRVSCGV (SEQ ID NO:8) with one, two, three or four conservative amino acid substitutions, CKTRVSCGV (SEQ ID NO:8) with one, two or three non-conservative amino acid substitution, or CKTRVSCGV (SEQ ID NO:8) with one, two or three non-conservative amino acid substitution and one, two, three or four conservative amino acid substitutions;
- (f) CAGRRSAYC (SEQ ID NO:9), CAGRRSAYC (SEQ ID NO:9) with one, two, three or four conservative amino acid substitutions, CAGRRSAYC (SEQ ID NO:9) with one, two or three non-conservative amino acid substitution, or CAGRRSAYC (SEQ ID NO:9) with one, two or three non-conservative amino acid substitution and one, two, three or four conservative amino acid substitutions;
- and
- (g) CSGGKVLDC (SEQ ID NO:11), CSGGKVLDC (SEQ ID NO:11) with one, two, three or four conservative amino acid substitutions, CSGGKVLDC (SEQ ID NO:11) with one, two or three non-conservative amino acid substitution, or CSGGKVLDC (SEQ ID NO:11) with one, two or three non-conservative amino acid substitution and one, two, three or four conservative amino acid substitutions;
- and
- (h) XRTX (SEQ ID NO:60), where X is R or K (SEQ ID NOs:12-15), wherein the amino acid sequence is not CGNKRTRGC (SEQ ID NO:16), CNRRTKAGC (SEQ ID NO:17) or CNKRTRGGC (SEQ ID NO:18)i
- (i) CLSDGK (SEQ ID NO:2) with one, two or three conservative amino acid substitutions, CLSDGK (SEQ ID NO:2) with one non-conservative amino acid substitution, or CLSDGK (SEQ ID NO:2) with one non-conservative amino acid substitution and one, two or three conservative amino acid substitutions;
- wherein the peptide selectively binds to tumor lymphatics.
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A method of identifying an agent that targets tumor lymphatics, the method comprising:
- (a) contacting non-cancerous tissue with a library of candidate agents under conditions sufficient to allow for selective binding of agents to the non-cancerous tissue,
- (b) collecting candidate agents that do not bind non-cancerous tissue from step (a),
- (c) contacting cancerous or pre-malignant tissue with the candidate agents collected in step (b) under conditions sufficient to allow for selective binding of agents to the cancerous or pre-malignant tissue, and
- (d) collecting candidate agents bound to lymphatic endothelial cells from the cancerous or pre-malignant tissue, wherein binding of candidate agents to lymphatic endothelial cells to the cancerous or pre-malignant tissue identifies the candidate agent as an agent that targets tumor lymphatics.
1 more element
Dependencies are inferred from the claim text.