Bacillus Calmette-Guerin (BCG) and antigen presenting cells for treatment of bladder cancer
Combination therapeutics for the treatment of cancer include the use of immune effector cells, IL-15 based superagonists and one or more immunotherapeutic agents such as Bacillus Calmette-Guerin (BCG).
1. A method of treating urothelial/bladder carcinoma, comprising:
administering to a subject having urothelial/bladder carcinoma an effective dose of an immunotherapeutic agent; and,
isolating an immune effector cell from a urine sample of the subject;
culturing the immune effector cells with a composition comprising an IL-15:IL-15Rα fusion protein complex,
reinfusing the cultured immune effector cells to the subject,
thereby treating the carcinoma.
2. The method of claim 1 wherein the composition comprises an IL-15N72D:IL-15RαSu/Fc complex.
3. The method of claim 1 , wherein the immunotherapeutic agent comprises Bacillus Calmette-Guerin (BCG).
4. The method of claim 1 , wherein the immune effector cell comprises T cells, B cells, natural killer (NK) cells, natural killer T (NK-T) cells, dendritic cells, mast cells, myeloid-derived phagocytes or combinations thereof.
5. The method of claim 4 , wherein the immune effector cell is a dendritic cell.
6. The method of claim 1 , wherein the IL-15:IL-15Rα fusion protein complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
7. The method of claim 1 , further comprising culturing the immune effector cells with urothelial/bladder carcinoma antigens.
8. A method of inducing an anti-bladder cancer immune response in a subject in need thereof, comprising:
administering to the subject an effective dose of Bacillus Calmette-Guerin (BCG);
isolating dendritic cells from a urine sample of the subject;
culturing the dendritic cells with a composition comprising an IL-15:IL-15Rα fusion protein complex,
reinfusing the dendritic cells to the subject,
thereby inducing an anti-bladder cancer immune response.
9. The method of claim 8 wherein the composition comprises an IL-15N72D:IL-15RαSu/Fc complex.
10. The method of claim 9 , wherein the IL-15N72D:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
11. The method of claim 8 , further comprising administering one or more chemotherapeutic agents.
12. The method of claim 8 further comprising culturing the dendritic cells with urothelial/bladder carcinoma antigens.
13. The method of claim 1 , wherein the composition comprises an IL-15N72D:IL-15RαSu/Fc complex, wherein the complex is N-803 and wherein the immunotherapeutic agent is BCG.
14. The method of claim 9 , wherein the complex is N-803.