Compositions and methods for the prevention and treatment of cancer
Conventional cancer immunotherapy falls short at efficiently expanding T cells that specifically target cancerous cells in numbers sufficient to significantly reduce the tumor size or cancerous cell number in vivo. To overcome this limitation, provided herein are nanoparticles coated with MHC class I and/or class II molecules presenting tumor-specific antigens and co-stimulatory molecules and their use to expand antigen-specific anti-tumorigenic T cells to levels not achieved in current immunotherapeutic techniques. These antigen-specific anti-tumorigenic T cells include cytotoxic T cells, effector T cells, memory T cells, and helper T cells that are necessary to initiate and maintain a substantial immune response against metastatic or non-metastatic cancerous, pre-cancerous, or neoplastic cells in vivo. The present invention describes a systemic approach to targeting cancerous or pre-cancerous cells that are circulating cells, as in lymphomas, migratory metastatic cells, and solid tumors.
1. A method of treating a tumor or cancer in a subject and the cancer or tumor is amenable to treatment by an immune response, comprising administering to the subject a nanoparticle having a core diameter from about 1 nm to about 100 nm, wherein the nanoparticle comprises from about 10 to about 500 cancer or tumor relevant antigen/MHC complexes and co-stimulatory complexes, each operatively coupled to the nanoparticle, wherein the ratio of co-stimulatory complexes to the antigen/MHC complexes on the nanoparticle is from about 0.1:1 to about 50:1, and the nanoparticle is administered in an amount sufficient to provide an expanded population of antigen-specific anti-tumorigenic T cells specific to the tumor or cancer, thereby treating the tumor or cancer, and wherein the MHC molecule of the antigen/MHC complex comprises either or both MHC class I and MHC class II molecules.
2. The method of claim 1 , wherein said expanded population of anti-tumorigenic T cells are antigen-specific anti-tumorigenic effector T cells, circulating antigen-specific CD8+ T cells and/or CD4+ T cells.
3. The method of claim 1 , wherein the nanoparticle core has a diameter from about 1 nm to about 50 nm or from about 1 to about 30 nm.
4. The method of claim 1 , wherein the population of antigen-specific anti-tumorigenic T cells comprise CD8+ T cells.
5. A method for inhibiting the growth of a tumor or for treating cancer in a patient and the cancer or tumor is amenable to treatment by an immune response, by administering to the patient a nanoparticle having a core diameter from about 1 nm to about 100 nm, wherein the nanoparticle comprises from about 10 to about 500 disease or tumor relevant antigen/MHC complexes and co-stimulatory complexes, each operatively coupled to the nanoparticle, wherein the ratio of co-stimulatory complexes to antigen/MHC complexes on the nanoparticle is from about 0.1:1 to about 50:1, and the nanoparticle is administered to the patient in an amount sufficient to expand antigen-specific anti-tumorigenic T cells, and wherein the MHC molecule of the complex comprises either or both MHC class I and MHC class II molecules.
6. The method of claim 5 wherein the antigen-specific anti-tumorigenic T cells comprise memory T cells, circulating antigen-specific CD8 + T cells and/or CD4 + T cells.
7. The method of claim 5 , wherein the nanoparticle has a core diameter from about 1 nm to about 50 nm or from about 1 nm to about 30 nm.
8. The method of claim 5 , wherein antigen-specific anti-tumorigenic T cells comprise CD8+ and/or CD4 + .
9. The method of claim 4 , wherein the expanded population comprises from about 5% to about 90% of total circulating T cells.
10. The method of claim 9 , wherein the expanded population comprises from about 10% to about 50% of total circulating T cells.
11. The method of claim 10 , wherein the expanded population comprises from about 17% to about 47% of total circulating T cells.
12. The method of claim 10 , wherein the expanded population comprises from about 20% to about 50% of total circulating T cells.
13. The method of claim 1 or 5 , wherein said nanoparticle is covalently bound to the co-stimulatory molecule and antigen/MHC complex and further wherein said binding is optionally via a linker.
14. The method of claim 13 , wherein the linker comprises ethylene glycol.
15. The method of claim 13 , wherein the co-stimulatory molecule is a co-stimulatory molecules that targets a receptor selected from the group of the CD28 receptor (CD80(B7.1), CD86(b7.2)), 4-IBBL, CD40, IL-15/IL15Ra, and ICOS.
16. The method of claim 1 or 5 , wherein the cancer or tumor is a melanoma or a lung cancer.
17. The method of claim 1 or 5 , wherein:
the nanoparticle has a core diameter of from about 1 nm to about 50 nm or from about 1 to about 30 nm; and
wherein when the cancer or tumor is melanoma, the antigen of the antigen/MHC complex is a melanoma-relevant antigen, or wherein when the cancer or tumor is lung cancer, the antigen of the antigen/MHC complex is a lung-cancer relevant antigen.
18. The method of claim 17 , wherein the co-stimulatory molecule is a co-stimulatory molecules that targets a receptor selected from the group of the CD28 receptor (CD80(B7.1), CD86(b7.2)), 4-IBBL, CD40, IL-15/IL15Ra, and ICOS.
19. The method of claim 1 or 5 , wherein the costimulatory molecules operatively coupled to the nanoparticle are identical or different.