IL-9 secreting CD8+ Tc9 cells and methods of treating cancer
A method of producing a population of CD8+ Tc9 lymphocytes is provided including priming a population of naïve CD8+ T cells by contacting the population of naïve CD8+ T cells with an immunogenic peptide, in the presence of a Tc9 supportive environment, thereby producing a population of CD8+ Tc9 lymphocytes which secrete IL-9. Purified populations of CD8+ Tc9 cells are also disclosed herein, as are method for their use in the treatment of cancer in a subject.
1. A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of a population of CD8+ Tc9 cells and a pharmaceutically acceptable carrier, wherein the population of CD8+ Tc9 cells secretes IL-9, wherein the CD8+ Tc9 cells are produced by priming a population of naïve CD8+ T cells by contacting the population of naïve CD8+ T cells with an immunogenic peptide, in the presence of a first Tc9 supportive environment, thereby producing a population of CD8+ Tc9 lymphocytes which secrete IL-9, wherein the first Tc9 supportive environment comprises at least one Tc9 polarizing cytokine or agent selected from the group consisting of IL-4, TGF-β, INF-γ neutralizing agent and IL-12 neutralizing agent.
2. The method of claim 1 , wherein the subject is a human.
3. The method of claim 1 , wherein the CD8+ Tc9 cells are produced from a population of autologous naïve CD8+ T cells.
4. The method of claim 1 , wherein the first Tc9 supportive environment comprises about 1 ng/ml to about 100 ng/ml of IL-4, about 0.1 ng/ml to about 10 ng/ml of TGF-β, about 1 μg/ml to about 100 μg/ml of anti-INF-γ monoclonal antibodies, and about 1 μg/ml to about 100 μg/ml of anti-IL-12 monoclonal antibodies.
5. The method of claim 1 , further comprising allowing the primed population of CD8+ Tc9 lymphocytes to proliferate in a second Tc9 supportive environment before administering the population of cells to the subject, wherein the second Tc9 supportive environment comprises about 1 ng/ml to about 100 ng/ml of IL-2.
6. The method of claim 1 , wherein the immunogenic peptide is presented on irradiated immunogenic peptide-loaded dendritic cells.
7. The method of claim 1 , wherein the cancer is selected from the group consisting of gastrointestinal cancer, ovarian cancer, breast cancer, head and neck cancer, lung cancer, cancer of the nervous system, kidney cancer, retinal cancer, melanoma, stomach cancer, liver cancer, pancreatic cancer, genital-urinary cancer, colorectal cancer, and bladder cancer.
8. The method of claim 1 , wherein the cancer is a selected from colorectral cancer and melanoma.
9. The method of claim 1 , wherein the population of CD8+ Tc9 cells is administered to the subject intravenously.
10. The method of claim 1 , further comprising the administration of a chemotherapeutic agent to the subject.
11. The method of claim 10 , the chemotherapeutic agent comprising cyclophosphamide.