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 course of therapy to an individual previously diagnosed with cancer by parenteral administration of an effective dose of up to 5 mg/kg of an active agent consisting of an annexin V protein, wherein the annexin V protein consists of an amino sequence which has at least 95% sequence identity to the amino acid sequence of human annexin V protein in a combination therapy with a second anti-cancer agent, wherein the administering is performed by a route that provides for a circulating half-life of at least about 1 hour.
2. The method of claim 1 , wherein the tumor is a carcinoma.
3. A method of increasing the immune response to a tumor positive for surface phosphatidylserine in an individual, the method comprising: administering a course of therapy of an effective dose of from 50 g/kg to 5 mg/kg human annexin V protein to an individual previously diagnosed with cancer, wherein administration is parenteral and provides for a circulating half-life of at least 3 hours, in combination with radiation therapy, and wherein the combination therapy provides for a synergistic effect.
4. The method of claim 1 , wherein the effective dose is administered at least twice.
5. The method of claim 1 , wherein the combination therapy provides for a synergistic effect.
6. The method of claim 1 , wherein the second anti-cancer agent is an immune checkpoint inhibitor, where the combination therapy provides for a synergistic effect.
7. A method of increasing the immune response to a tumor positive for surface phosphatidylserine in an individual, the method comprising:
administering a course of therapy of an effective dose of from 50 μg/kg to 5 mg/kg human annexin V protein wherein administration is by osmotic pump, and provides for a circulating half-life of at least 3 hours, in combination with radiation therapy, wherein the combination therapy provides for a synergistic effect.
8. The method of claim 1 , wherein the tumor is positive for expression of surface Phosphatidylserine.
9. The method of claim 8 , wherein the presence of a tumor positive for surface expression of Phosphatidylserine is determined by imaging with an annexin V agent.
10. The method of claim 1 , wherein the annexin V protein consists of an amino sequence which has at least 99% sequence identity to the amino acid sequence of wild-type human annexin V.
11. The method of claim 1 , wherein the annexin V protein is a recombinant annexin V protein.
12. A method of increasing the immune response to a tumor positive for surface phosphatidylserine in an individual, the method comprising: administering to an individual previously diagnosed with cancer an effective dose of up to 5 mg/kg of an active agent consisting of an annexin V polypeptide, wherein the annexin V polypeptide consists of an amino sequence which has at least 95% sequence identity to the amino acid sequence of human annexin V protein, by parenteral administration providing for a circulating half-life of at least 3 hours, in a combination therapy with an immune checkpoint inhibitor, wherein the combination therapy provides for a synergistic effect.
13. The method of claim 12 , further comprising:
administering to the individual radiation therapy.