Peptide saporin conjugate for the treatment of cancer
Disclosed herein, are compositions comprising one or more molecular guidance system (MGS) peptides and a cytotoxic agent. Also described herein, are methods of administering the compositions to patients with cancer.
1. A composition comprising one or more molecular guidance system (MGS) peptide(s) covalently attached to a cytotoxic agent, directly or through a linker, wherein the MGS peptide(s) is/are selected from SEQ ID NO: 3, 6, 33, 73, 74, 80, 81, 82, and 84.
2. The composition of claim 1 , wherein the cytotoxic agent is saporin.
3. The composition of claim 1 , wherein the composition comprises two MGS peptides conjugated to one or more cytotoxic agents via one or more chemical linkers, wherein the linkers are covalently linked to one another to form a dimeric structure, and wherein the peptides are not directly linked to each other.
4. The composition of claim 1 , wherein the composition comprises four MGS peptides conjugated to one or more cytotoxic agents via one or more chemical linkers, wherein the linkers are covalently linked to one another and form a tetrameric structure, and wherein the peptides are not directly linked to each other.
5. The composition of claim 1 , wherein the MGS peptide is SEQ ID NO:3 and the cytotoxic agent is saporin.
6. The composition of claim 1 , wherein the linker comprises polyethylene glycol (PEG).
7. The composition of claim 1 , wherein the MGS peptide is SEQ ID NO: 80, wherein the peptide is covalently attached to PEG; wherein the cytotoxic agent is saporin, and wherein the saporin is covalently attached to PEG directly or through a linker.
8. A pharmaceutical composition comprising the composition of any one of claims 1 , and 7 and a pharmaceutically acceptable carrier.
9. A method of treating a cancer, the method comprising: (a) identifying a patient in need of treatment; (b) administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 8 , wherein the cancer is lung cancer, breast cancer, colorectal cancer, ovarian cancer, or pancreatic cancer.
10. The method of claim 9 , wherein the cancer is a primary, secondary, refractory, or relapsing tumor.
11. The method of claim 9 , further comprising administering to the patient a therapeutically effective amount of radiation therapy, immunotherapy, chemotherapy, or a combination thereof.
12. A method of targeting an intracellular target, the method comprising administering one or more MGS peptide(s) covalently attached to a cytotoxic agent directly or through a linker, wherein the MGS peptide(s) is/are selected from SEQ ID NO: 3, 6, 33, 73, 74, 80, 81, 82, and 84, and wherein the cytotoxic agent targets an intracellular target.
13. The method of claim 12 , wherein the intracellular target is the lysosome.
14. An MGS peptide selected from SEQ ID NO: 3, 6, 33, 73, 74, 80, 81, 82, and 84.
15. The method of claim 12 , wherein the MGS peptide is SEQ ID NO: 80, wherein the peptide is covalently attached to PEG; the cytotoxic agent is saporin, and wherein the saporin is covalently attached to PEG directly or through a linker.
16. The method of claim 9 , wherein the MGS peptide is SEQ ID NO: 80, wherein the peptide is covalently attached to PEG; the cytotoxic agent is saporin, and wherein the saporin is covalently attached to PEG directly or through a linker.
17. The composition of claim 3 or 4 , wherein the MGS peptide is selected from SEQ ID NO. 80, 81, 82, and 84.
18. The pharmaceutical composition of claim 8 , wherein the cytotoxic agent is a toxin.