Compositions and methods for treating diseases by inhibiting exosome release
A multipartite peptide that inhibits release of exosomes in a cell, comprising an N-terminal end and a C-terminal end and comprising at least one secretion modifying region (SMR) peptide from HIV-1 Nef and at least one Clusterin (Clu)-binding peptide (Clu-BP). Pharmaceutical compositions comprising these peptides alone or in synergistic combinations with other active agents in methods for treating cancers and/or infectious diseases are further provided herein.
1. A multipartite peptide that inhibits release of exosomes in a cell,
wherein the peptide comprises an amino acid sequence selected from the group consisting of VGFPVAAVGFPVHPLSKHPYWSQP (SEQ ID NO:6), VGFPVAAVGFPVAAHPLSKHPYWSQP (SEQ ID NO:7), and VGFPVAAVGFPVAAHPLSKHPYWSQPAAHPLSKHPYWSQP (SEQ ID NO:8).
2. A polynucleotide encoding the multipartite peptide of claim 1 .
3. An expression vector comprising the polynucleotide of claim 2 operably linked to a regulatory sequence.
4. A cell comprising the expression vector of claim 3 .
5. A pharmaceutical composition comprising the multipartite peptide of claim 1 and a pharmaceutically acceptable carrier.
6. The pharmaceutical composition of claim 5 , wherein the multipartite peptide is pegylated.
7. The pharmaceutical composition of claim 5 , wherein the multipartite peptide is further linked to an endopeptidase cleavage signal.
8. A method for treating a cancer, comprising:
administering to a subject in need of such treatment an effective amount of the pharmaceutical composition of claim 5 .
9. The method of claim 8 , wherein the subject has breast cancer.
10. The method of claim 8 , further comprising the step of administering to the subject a chemotherapeutic agent.
11. The method of claim 10 , wherein the chemotherapeutic agent is paclitaxel or cisplatin.
12. A method for treating an infectious disease, comprising:
administering to a subject in need of such treatment an effective amount of the pharmaceutical composition of claim 5 .
13. The method of claim 12 , wherein the subject is infected with HIV-1 or HIV-2.