TARGETED CANCER THERAPY
Some embodiments of the present disclosure are directed to methods that include delivering to a subject a papillomavirus particle or soluble papillomavirus protein that targets a tumor, and delivering to the subject an immune cell expressing a receptor that binds to a surface antigen of the papillomavirus particle or soluble papillomavirus protein, respectively.
1 . A method comprising
delivering to a subject a papillomavirus particle or soluble papillomavirus protein that targets a tumor, and
delivering to the subject an immune cell expressing a receptor that binds to a surface antigen of the papillomavirus particle or soluble papillomavirus protein, respectively.
2 . The method of claim 1 , wherein the papillomavirus particle is a papilloma virus-like particle or a papilloma pseudovirus.
3 . The method of claim 1 , wherein the papillomavirus particle or soluble papillomavirus protein is a human papillomavirus particle or a soluble human papillomavirus protein.
4 . The method of claim 1 , wherein the papillomavirus particle or soluble papillomavirus protein is a modified human papillomavirus particle or a soluble modified human papillomavirus protein.
5 . The method of claim 1 , wherein the papillomavirus particle or soluble papillomavirus protein is a non-human papillomavirus particle or a soluble non-human papillomavirus protein.
6 . The method of claim 4 , wherein the non-human papillomavirus particle is a bovine, murine, cotton-rabbit, macaque or rhesus papillomavirus particle or soluble papillomavirus protein.
7 . The method of claim 6 , wherein the non-human papillomavirus particle or soluble non-human papillomavirus protein is a bovine papillomavirus particle or soluble bovine papillomavirus protein.
8 . The method of claim 1 , wherein the papillomavirus particle is a papilloma virus-like particle.
9 . The method of claim 1 , wherein the papillomavirus particle is a papilloma pseudovirus.
10 . The method of claim 1 , wherein the soluble papillomavirus protein forms a capsomer.
11 . The method of claim 1 , wherein the capsomer comprises of L1 protein.
12 . The method of claim 1 , wherein the immune cell is leukocyte.
13 . The method of claim 12 , wherein the leukocyte is a neutrophil, eosinophil, basophil, lymphocyte or a monocyte.
14 . The method of claim 13 , wherein the leukocyte is a lymphocyte.
15 . The method of claim 14 , wherein the lymphocyte is a T cell, a B cell, an NK cell, or an NKT cell.
16 . The method of claim 15 , wherein the lymphocyte is a T cell.
17 . The method of claim 1 , wherein immune cell is a dendritic cell.
18 . The method of claim 1 , wherein the receptor is a recombinant antigen receptor.
19 . The method of claim 1 , wherein the receptor is a chimeric antigen receptor.
20 . The method of claim 1 , wherein the surface antigen of the papillomavirus particle is an L1 protein or an L1/L2 protein complex.
21 . The method of claim 1 , wherein the surface antigen is covalently linked to a surface of the papillomavirus particle.
22 . The method of claim 21 , wherein the surface antigen is a hapten.
23 . The method of claim 1 , wherein the surface antigen is non-covalently linked to a surface of the papillomavirus particle.
24 . The method of claim 1 , wherein the surface antigen is a peptide incorporated into a region of a recombinant capsid protein that is surface-exposed in the papillomavirus particle.
25 . The method of claim 1 , wherein the surface antigen of the papillomavirus is a self-antigen.
26 . The method of claim 1 , wherein the surface antigen of the papillomavirus is a non-self antigen.
27 . The method of claim 26 , wherein the non-self antigen is a bacterial, yeast, protozoan or viral antigen.
28 . The method of claim 1 , wherein the surface antigen of the papillomavirus is a tumor antigen.
29 . The method of claim 28 , wherein the tumor antigen is a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA).
30 . The method of claim 29 , wherein the tumor antigen is or comprises an epitope of CD19, CD20, CD21, CD22, CD45, BCMA, MART-1, MAGE-A3, glycoprotein 100 (gp100), NY-ESO-1, HER2 (ErbB2), IGF2B3, EGFRvIII, Kallikrein 4, KIF20A, Lengsin, Meloe, MUC-1, MUC5AC, MUC-16, B7-H3, B7-H6, CD70, CEA, CSPG4, EphA2, EpCAM, EGFR family, FAP, FRα, glupican-3, GD2, GD3, HLA-A1+MAGE1, IL-11Rα, IL-23Rα2, Lewis-Y, mesothelin, NKG2D ligands, PSMA, ROR1, survivin, TAG72 or VEGFR2.
31 . The method of claim 30 , wherein the tumor antigen is or comprises an epitope of CD19.
32 . The method of claim 30 , wherein the tumor antigen is selected from full length CD19, a fragment of CD19, at least one C2 Ig-like domain of CD19, or a linear epitope of CD19.
33 . The method of claim 1 , wherein the surface antigen of the papillomavirus is or comprises a synthetic epitope.
34 . The method of claim 33 , wherein the synthetic epitope is a His tag, a FLAG tag, or an SV5 tag.
35 . The method of claim 1 , wherein the papillomavirus particle, the immune cell or the papillomavirus particle and the immune cell are delivered via a parenteral, enteric or topical route.
36 . The method of claim 35 , wherein the parenteral route is intra-abdominal, intra-amniotic, intra-arterial, intra-articular, intrabiliary, intrabronchial, intrabursal, intracardiac, intracartilaginous, intracaudal, intracavernous, intracavitary, intracerebral, intracisternal, intracorneal, intracoronal, intracoronary, intracorporus, intracranial, intradermal, intradiscal, intraductal, intraduodenal, intradural, intraepidermal, intraesophageal, intragastric, intragingival, intraileal, intralesional, intraluminal, intralymphatic, intramedullary, intrameningeal, intramuscular, intraocular, intraovarian, intrapericardial, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intraocular, intrasinal, intraspinal, intrasynovial, intratendinous, intratesticular, intrathecal, intrathoracic, intratubular, intratumor, intratympanic, intrauterine, intravascular, intravenous (bolus or drip), intraventricular, intravesical or subcutaneous.
37 . The method of claim 1 , wherein the tumor is an ocular tumor, a melanoma, a head and neck tumor, a lung tumor, a bladder tumor, a breast tumor, a colorectal tumor, a gastric tumor, an ovarian tumor, a pancreatic tumor, a prostate tumor, a liver tumor, a renal tumor, or mesothelioma].
38 . A method comprising
delivering to a subject a virus that targets a tumor, and
delivering to the subject an immune cell comprising a receptor that binds to a surface antigen of the virus.