Nanoparticle compositions and methods for immunotherapy
The present invention provides compositions and methods for immunotherapy, which include shelf-stable pharmaceutical compositions for inducing antigen-specific T cells. Such compositions are employed as components of an artificial antigen presenting cell (aAPC), to provide a patient with complexes for presentation of an antigen (e.g., a tumor antigen) and/or a T cell co-stimulatory molecule.
1. A method of treating cancer, comprising:
administering to a cancer patient, either during, concomitantly, or after therapy with one or more checkpoint inhibitors, a composition comprising a nano-scale artificial antigen presenting cell (aAPC) comprising:
a nanoparticle having an average diameter of less than about 400 nm, comprising a hydrophilic sheath formed from polyethylene glycol (PEG) chains;
a population of anti-CD28 T cell costimulatory ligands on the surface of the nanoparticle; and
a population of MHC Class I antigen presenting complex ligands on the surface of the nanoparticle, wherein a tumor-associated antigenic peptide is bound to the MHC Class I antigen binding cleft; and wherein the costimulatory ligands and MHC class I antigen presenting complex ligands are attached to terminal ends of the PEG chains.
2. The method of claim 1 , wherein the cancer is a carcinoma.
3. The method of claim 1 , wherein the cancer is a melanoma.
4. The method of claim 1 , wherein the cancer is a lung cancer.
5. The method of claim 1 , wherein the cancer is a lymphoma.
6. The method of claim 1 , wherein the cancer is non-small cell lung carcinoma.
7. The method of claim 1 , wherein the cancer is a head and neck cancer.
8. The method of claim 1 , wherein the cancer is a renal cancer.
9. The method of claim 1 , wherein the checkpoint inhibitor is selected from an anti-CTLA4, or an anti-PD1, or an anti-PD-L1 antibody.
10. The method of claim 1 , wherein the checkpoint inhibitor is an anti-PD1 antibody.
11. The method of claim 1 , wherein the checkpoint inhibitor is an anti-PD-L1 antibody.
12. The method of claim 1 , wherein the checkpoint inhibitor is selected from Nivolumab, Pembrolizumab, and Ipilimumab.
13. The method of claim 1 , wherein the nanoparticles have a size in the range of about 20 to 200 nm.
14. The method of claim 13 , wherein the nanoparticles have a size in the range of about 100 to 200 nm.
15. The method of claim 1 , wherein the nano-aAPC is administered after about 1 to 8 weeks of checkpoint inhibitor therapy.
16. The method of claim 15 , wherein the nano-aAPC is administered after about 2 to 4 weeks of checkpoint inhibitor therapy.
17. The method of claim 1 , wherein the nano-aAPC is administered about once every four weeks.
18. The method of claim 1 , wherein the nano-aAPC is administered about once every two weeks.
19. The method of claim 1 , wherein the nano-aAPC is administered concomitantly with the checkpoint inhibitor therapy.
20. The method of claim 1 , wherein the patient received the checkpoint inhibitor therapy, and was resistant, only partially responsive, or transiently responsive to the checkpoint inhibitor therapy.
21. The method of claim 1 , wherein the nanoparticle comprises a PLGA or PLA polymer core and wherein the polymer core is based on 1:0 to 1:1 Lactic Acid:Glycolic Acid ratio.
22. The method of claim 1 , wherein the nanoparticle comprises a PLGA polymer core having about 1:1 Lactic Acid:Glycolic Acid.
23. The method of claim 1 , wherein the nanoparticle comprises a PLGA or PLA polymer core and the core polymer has a molecular weight of from about 10K to about 50K.
24. The method of claim 1 , wherein the nanoparticle comprises a PLGA or PLA polymer core, and PLGA-PEG and/or PLA-PEG block co-polymers, the PEG portion forming the hydrophilic shell.
25. The method of claim 24 , wherein the polypeptide ligands are attached through functional groups at the PEG terminus.
26. The method of claim 1 , wherein the nanoparticle comprises a PLGA or PLA polymer core and wherein the PLA-PEG co-polymer contains a PLA portion having a molecular weight of from about 10K to about 50K, and a PEG portion having molecular weight(s) of from about 2K to about 10K, or wherein the PLGA-PEG co-polymer contains a PLGA portion having molecular weight of from about 10K to about 50K, and a PEG portion having molecular weight(s) of from about 2K to about 10K.
27. The method of claim 26 , wherein the PLA portion of the PLA-PEG has a molecular weight of about 20K, and the PEG portion has a molecular weight of about 3K and/or about 5K, or wherein the PLGA-PEG has a molecular weight of about 20K, and the PEG portion has a molecular weight of about 3K and/or about 5K.
28. The method of claim 1 , wherein the population of MHC Class I antigen presenting complexes comprise an HLA amino acid sequence fused to each of two immunoglobulin sequences, each immunoglobulin sequence having a partial heavy chain sequence of a CH2 and CH3 domain and a hinge region, in the absence of a variable domain sequence and in the absence of a light chain sequence, wherein the HLA amino acid sequences are fused to the hinge regions.