Combination of an IL-2RBETA-selective agonist and a long-acting IL-15 agonist
In one or more embodiments of the invention, a method is provided, the method comprising the steps of administering to a cancer patient: (a) an IL-2Rβ-activating amount of a long-acting, IL-2Rβ-selective agonist; and (b) an IL-15R-activating amount of a long-acting, IL-15 moiety. In one or more embodiments of the invention, a composition is provided, the composition comprising: an IL-2Rβ-activating amount of a long-acting, IL-2Rβ-selective agonist; and an IL-15R-activating amount of a long-acting, IL-15 moiety. In one or more embodiments of the invention, a kit is provided, the kit comprising: an IL-2Rβ-activating amount of a long-acting, IL-2Rβ-selective agonist; an IL-15R-activating amount of a long-acting, IL-15 moiety; and instructions for use of the IL-2Rβ-selective agonist and the long-acting, IL-15 moiety.
1. A method of treating a patient suffering from a cancer, the method comprising the steps of:
(a) administering to the patient an IL-2Rβ-activating amount of a long-acting, IL-2Rβ-selective agonist comprised of an IL-2 moiety covalently attached to a water-soluble polymer having the formula:
wherein each n is an integer from 3 to 4000, or pharmaceutically acceptable salts thereof; and
(b) administering an IL-15 receptor-activating amount of a long-acting IL-15 agonist comprised of an IL-15 protein covalently attached to at least one water-soluble polymer having a formula selected from:
and
wherein n for each formula is an integer from 3 to 4000, or pharmaceutically acceptable salts thereof.
2. The method of claim 1 , wherein the patient is human.
3. The method of claim 1 , wherein the cancer is a solid cancer.
4. The method of claim 1 , wherein the solid cancer is selected from the group consisting of breast cancer, ovarian cancer, colon cancer, prostate cancer, colorectal cancer, gastric cancer, malignant melanoma, liver cancer, small cell lung cancer, non-small cell lung cancer, thyroid cancers, kidney cancer, cancer of the bile duct, brain cancer, cervical cancer, maxillary sinus cancer, bladder cancer, esophageal cancer, Hodgkin's disease and adrenocortical cancer.
5. The method of claim 3 , wherein the cancer is colon cancer.
6. The method of claim 3 , wherein the cancer is breast cancer.
7. The method of claim 1 , wherein step (a) is carried out prior to step (b) being carried out.
8. The method of claim 1 , wherein (a) is carried out after step (b) is carried out.
9. The method of claim 1 , wherein steps (a) and (b) are carried out simultaneously.
10. The method of claim 1 , wherein the IL-2 moiety is aldesleukin.
11. The method of claim 1 , wherein the polymer portion of the IL-2Rβ-selective agonist, including both poly(ethylene glycol) arms, has a weight-average molecular weight in a range of from 250 daltons to 90,000 daltons.
12. The method of claim 1 , wherein the polymer portion of the IL-2Rβ-selective agonist, including both poly(ethylene glycol) arms, has a weight-average molecular weight of 20,000 daltons.
13. The method of claim 1 , wherein n is selected such that the polymer portion of the IL-15 agonist, including both poly(ethylene glycol) arms, has a weight average molecular weight in a range of from 20,000 daltons to 90,000 daltons.
14. The method of claim 1 , wherein one, two, or three water-soluble polymers are attached to the IL-15 protein.