Use of annexin V as a method to block tumor induced immunosuppression of the innate immune response
View Patent ↗Methods are provided for treating a subject with cancer, with a therapeutic dose of annexin V to the subject.
1 . A method of increasing the immune response to a tumor in an individual, the method comprising:
administering a monotherapy consisting of an effective dose of an active agent consisting of biologically active annexin V protein to an individual previously diagnosed with cancer by parenteral administration;
wherein the annexin V protein consists of an amino sequence which has the amino acid sequence of SEQ ID NO: 1, or a biologically active phosphatidylserine-binding fragment thereof which has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1; and wherein the administration is delivered for a period of at least 30 minutes.
2 . The method of claim 1 , wherein the parenteral administration is intravenous administration.
3 . The method of claim 1 , wherein the tumor is positive for expression of surface phosphatidylserine.
4 . The method of claim 1 , wherein the effective dosage is of up to 20 mg/kg of the active agent.
5 . The method of claim 4 , wherein the effective dosage is of up to 5 mg/kg of the active agent.
6 . The method of claim 1 , wherein the annexin V protein is a biologically active phosphatidylserine-binding fragment of the annexin V protein that consists of the amino acid sequence of SEQ ID NO: 1, and wherein the biologically active phosphatidylserine-binding fragment consists of an amino sequence which has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1.
7 . The method of claim 1 , wherein the annexin V protein is a recombinant annexin V protein.
8 . The method of claim 1 , wherein the tumor is a solid tumor.
9 . The method of claim 1 , wherein the period is from 30 minutes to 24 hours.
10 . A method of increasing the immune response to a tumor in an individual, the method comprising:
administering a monotherapy consisting of an effective dose of an active agent consisting of biologically active annexin V protein to an individual previously diagnosed with cancer by parenteral administration;
wherein the annexin V protein consists of an amino sequence which has the amino acid sequence of SEQ ID NO: 1, or a biologically active phosphatidylserine-binding fragment thereof which has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1.
11 . The method of claim 10 , wherein the parenteral administration is intravenous administration.
12 . The method of claim 10 , wherein the tumor is positive for expression of surface phosphatidylserine.
13 . The method of claim 10 , wherein the effective dosage is of up to 20 mg/kg of the active agent.
14 . The method of claim 13 , wherein the effective dosage is of up to 5 mg/kg of the active agent.
15 . The method of claim 10 , wherein the annexin V protein is a biologically active phosphatidylserine-binding fragment of the annexin V protein that consists of the amino acid sequence of SEQ ID NO: 1, and wherein the biologically active phosphatidylserine-binding fragment consists of an amino sequence which has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 1.
16 . The method of claim 10 , wherein the annexin V protein is a recombinant annexin V protein.
17 . The method of claim 10 , wherein the tumor is a solid tumor.
18 . The method of claim 1 , wherein the annexin V protein comprises a post-expression modification.
19 . The method of claim 18 , wherein the post-expression modification comprises PEGylation.
20 . The method of claim 1 , wherein the annexin V protein is fused to another polypeptide.
21 . The method of claim 20 , wherein the other polypeptide is stable plasma protein that is able to extend the in vivo plasma half-life of annexin V.
22 . The method of claim 1 , wherein the annexin V protein is modified by chemical derivatization.
23 . The method of claim 10 , wherein the annexin V protein comprises a post-expression modification.
24 . The method of claim 23 , wherein the post-expression modification comprises PEGylation.
25 . The method of claim 10 , wherein the annexin V protein is fused to another polypeptide.
26 . The method of claim 25 , wherein the other polypeptide is stable plasma protein that is able to extend the in vivo plasma half-life of annexin V.
27 . The method of claim 10 , wherein the annexin V protein is modified by chemical derivatization.
28 . The method of claim 10 , wherein the administration is performed by a route that provides for a circulating half-life of at least 1 hour.
29 . The method of claim 28 , wherein the circulating half-life of at least 3 hours.