Treatment of immune evasive tumors
The present disclosure provides methods of treating immune evasive cancers using surface functionalized particles alone or in combination with cancer therapeutics.
1 . A method for treating a subject having an immune evasive cancer and who had previously received immunotherapy or in which the cancer is refractory to immunotherapy, comprising administering to the subject negatively charged particles alone or in combination with a cancer therapeutic, wherein the negatively charged particles comprise: a polyglycolic acid (PGA) polymer, polylactic acid (PLA), poly (lactic-co-glycolic acid) (PLGA), polystyrene, chitosan, polysaccharide, one or more lipids, diamond, iron, zinc, cadmium, gold, silver, or any combination thereof, wherein the particles have a zeta potential between −30 to −100 mV and a size greater than 200 nm and are free from one or more therapeutic agent,
wherein the cancer therapeutic is selected from the group consisting of a growth inhibitor, DNA-replication inhibitor, kinase inhibitor, receptor tyrosine kinase inhibitor, signaling cascade inhibitor, angiogenesis inhibitor, metabolic inhibitor, amino acid synthesis inhibitor, selective inhibitor of oncogenic protein, inhibitor of metastasis, inhibitor of anti-apoptosis factor, apoptosis inducer, enzyme inhibitor, nucleoside stimulating inhibitor, antibody-drug conjugate, DNA-damaging agent, cytokines, one or more cell-based therapies, a hormone therapy, one or more cancer vaccines, or one or more immunotherapies selected from the group consisting of: oncolytic virus, oncolytic bacteria or other bacterial compositions, Bacillus Calmette-Guerin (BCG), microbiome modulator, Stimulator of interferon genes (STING) pathway modulator, and toll-like receptor (TLR) modulator.
2 . The method of claim 1 , wherein the negatively charged particles are poly (lactic-co-glycolic acid) (PLGA) particles.
3 . The method of claim 1 , wherein the negatively charged particles comprise polylactic acid:poly glycolic acid at a ratio from 80:20 to 20:80 poly glycolic acid: poly lactic acid.
4 . The method of claim 1 , wherein the negatively charged particles comprise one or more carboxyl groups.
5 . The method of claim 1 , wherein the negatively charged particles have a zeta potential between −80 mV and −30 mV.
6 . The method of claim 1 , wherein the diameter of the negatively charged particles is between 300 nm to 1000 nm.
7 . The method of claim 1 , wherein the subject has one or more immunologically cold tumors, one or more tumors with a low tumor mutational burden, one or more microsatellite stable tumors, one or more tumors with low microsatellite instability, and/or one or more tumors with a low tumor immune cell infiltrate.
8 . The method of claim 1 , wherein the administering transforms an immunologically cold tumor into an immunologically hot tumor.
9 . The method of claim 1 , wherein the administering reduces tumor size and/or inhibits tumor growth.
10 . The method of claim 1 , wherein the subject has a cancer selected from the group consisting of brain cancer, skin cancer, eye cancer, breast cancer, prostate cancer, pancreatic cancer, lung cancer, esophageal cancer, head and neck cancer, cervical cancer, liver cancer, colorectal cancer, bone cancer, uterine cancer, ovarian cancer, bladder cancer, endometrial cancer, stomach cancer, gastric cancer, oral cancer, thyroid cancer, kidney cancer, testicular cancer, leukemia, lymphoma, and mesothelioma.
11 . The method of claim 1 , comprising the combination with the cancer therapeutic,
wherein the cancer therapeutic comprises a growth inhibitor, DNA-replication inhibitor, kinase inhibitor, signaling cascade inhibitor, metabolic inhibitor, amino acid synthesis inhibitor, selective inhibitor of oncogenic protein, inhibitor of metastasis, inhibitor of anti-apoptosis factor, apoptosis inducer, enzyme inhibitor, nucleoside signaling inhibitor, antibody-drug conjugate, DNA-damaging agent, cytokines, angiogenesis inhibitor, or a receptor tyrosine kinase inhibitor.
12 . The method of claim 1 , comprising the combination with the cancer therapeutic, wherein the cancer therapeutic comprises one or more cell-based therapies selected from adoptive cell transfer, tumor-infiltrating leukocyte therapy, chimeric antigen receptor T-cell therapy (CAR-T), NK-cell therapy or stem cell therapy.
13 . The method of claim 1 , comprising the combination with the cancer therapeutic, wherein the cancer therapeutic comprises a hormone therapy.
14 . The method of claim 1 , comprising the combination with the cancer therapeutic, wherein the cancer therapeutic comprises one or more cancer vaccines.
15 . The method of claim 1 , comprising the combination with the cancer therapeutic, wherein the cancer therapeutic comprises one or more immunotherapies selected from the group consisting of: oncolytic virus, oncolytic bacteria or other bacterial compositions, Bacillus Calmette-Guerin (BCG), microbiome modulator, Stimulator of interferon genes (STING) pathway modulator, and toll-like receptor (TLR) modulator.
16 . The method of claim 1 , wherein the negatively charged particles and/or the cancer therapeutic is administered once daily, twice daily, three times per day, seven times per week, six times per week, five times per week, four times per week, three times per week, twice weekly, once weekly, once every two weeks, once every three weeks, once every 4 weeks, once every two months, once every three months, once every 6 months or once per year, and wherein the administering of the negatively charged particles and/or the cancer therapeutic comprises intravenous, oral, nasal, intramuscular, ocular, transdermal, or subcutaneous administration.
17 . The method of claim 16 , comprising the negatively charged particles, wherein the negatively charged particles are administered once weekly.
18 . The method of claim 1 , wherein the negatively charged particles are PLGA particles having a zeta potential between −80 to −30 mV and a diameter between 200 and 2000 nm.