KR102474924B1 - Adjuvant composition for cancer immunotherapy comprising Escherichia coli adhesion portion FimH - Google Patents
Adjuvant composition for cancer immunotherapy comprising Escherichia coli adhesion portion FimH Download PDFInfo
- Publication number
- KR102474924B1 KR102474924B1 KR1020200048612A KR20200048612A KR102474924B1 KR 102474924 B1 KR102474924 B1 KR 102474924B1 KR 1020200048612 A KR1020200048612 A KR 1020200048612A KR 20200048612 A KR20200048612 A KR 20200048612A KR 102474924 B1 KR102474924 B1 KR 102474924B1
- Authority
- KR
- South Korea
- Prior art keywords
- cancer
- fimh
- antigen
- preventing
- composition
- Prior art date
Links
- 241000588724 Escherichia coli Species 0.000 title claims abstract description 37
- 239000000203 mixture Substances 0.000 title claims abstract description 37
- 239000002671 adjuvant Substances 0.000 title description 7
- 238000002619 cancer immunotherapy Methods 0.000 title description 2
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 52
- 201000011510 cancer Diseases 0.000 claims abstract description 46
- 239000000427 antigen Substances 0.000 claims abstract description 44
- 108091007433 antigens Proteins 0.000 claims abstract description 44
- 102000036639 antigens Human genes 0.000 claims abstract description 44
- 239000004480 active ingredient Substances 0.000 claims abstract description 32
- 101710126013 Type 1 fimbrin D-mannose specific adhesin Proteins 0.000 claims abstract description 25
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 7
- 201000005202 lung cancer Diseases 0.000 claims abstract description 7
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 7
- 210000004027 cell Anatomy 0.000 claims description 29
- 108010058846 Ovalbumin Proteins 0.000 claims description 21
- 229940092253 ovalbumin Drugs 0.000 claims description 17
- 241000700605 Viruses Species 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 201000001441 melanoma Diseases 0.000 claims description 14
- 230000036541 health Effects 0.000 claims description 13
- 210000002919 epithelial cell Anatomy 0.000 claims description 10
- 235000013376 functional food Nutrition 0.000 claims description 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 9
- 201000009030 Carcinoma Diseases 0.000 claims description 8
- 230000001093 anti-cancer Effects 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- 108091034117 Oligonucleotide Proteins 0.000 claims description 4
- 201000010208 Seminoma Diseases 0.000 claims description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 4
- 229940022399 cancer vaccine Drugs 0.000 claims description 4
- 150000001720 carbohydrates Chemical class 0.000 claims description 4
- 235000014633 carbohydrates Nutrition 0.000 claims description 4
- 150000002632 lipids Chemical class 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 102000039446 nucleic acids Human genes 0.000 claims description 4
- 150000007523 nucleic acids Chemical class 0.000 claims description 4
- 108010042234 peptide SVYDFFVWL Proteins 0.000 claims description 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 4
- 239000007929 subcutaneous injection Substances 0.000 claims description 4
- 238000010254 subcutaneous injection Methods 0.000 claims description 4
- 208000001608 teratocarcinoma Diseases 0.000 claims description 4
- 238000009566 cancer vaccine Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007928 intraperitoneal injection Substances 0.000 claims description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 206010023347 Keratoacanthoma Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 206010042971 T-cell lymphoma Diseases 0.000 claims description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 208000007538 neurilemmoma Diseases 0.000 claims description 2
- 201000008968 osteosarcoma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 2
- 206010039667 schwannoma Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 2
- 208000017572 squamous cell neoplasm Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims 1
- 210000004443 dendritic cell Anatomy 0.000 abstract description 22
- 230000000694 effects Effects 0.000 abstract description 16
- 239000003623 enhancer Substances 0.000 abstract description 14
- 238000011282 treatment Methods 0.000 abstract description 11
- 241000282414 Homo sapiens Species 0.000 abstract description 10
- 210000001744 T-lymphocyte Anatomy 0.000 abstract description 9
- 210000005259 peripheral blood Anatomy 0.000 abstract description 9
- 239000011886 peripheral blood Substances 0.000 abstract description 9
- 230000004913 activation Effects 0.000 abstract description 5
- 230000002708 enhancing effect Effects 0.000 abstract description 4
- 230000005965 immune activity Effects 0.000 abstract description 4
- 230000005904 anticancer immunity Effects 0.000 abstract description 3
- 238000007920 subcutaneous administration Methods 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 2
- 238000011394 anticancer treatment Methods 0.000 abstract description 2
- 230000009775 lung immunity Effects 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 18
- 239000002158 endotoxin Substances 0.000 description 12
- 229960005486 vaccine Drugs 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 11
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 10
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 10
- 210000001165 lymph node Anatomy 0.000 description 10
- 210000004072 lung Anatomy 0.000 description 9
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 8
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 7
- 241000700159 Rattus Species 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 102000008070 Interferon-gamma Human genes 0.000 description 5
- 108010074328 Interferon-gamma Proteins 0.000 description 5
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 5
- 229960003130 interferon gamma Drugs 0.000 description 5
- 208000035473 Communicable disease Diseases 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 241000709661 Enterovirus Species 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000005907 cancer growth Effects 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100022297 Integrin alpha-X Human genes 0.000 description 2
- 241000701945 Parvoviridae Species 0.000 description 2
- 241000702670 Rotavirus Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 244000309743 astrovirus Species 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- JVJGCCBAOOWGEO-RUTPOYCXSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-4-amino-2-[[(2s,3s)-2-[[(2s,3s)-2-[[(2s)-2-azaniumyl-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxylatobutanoyl]amino]-6-azaniumy Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 JVJGCCBAOOWGEO-RUTPOYCXSA-N 0.000 description 1
- LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 description 1
- 208000021769 Acute sensory ataxic neuropathy Diseases 0.000 description 1
- 241000701242 Adenoviridae Species 0.000 description 1
- 241000701386 African swine fever virus Species 0.000 description 1
- WQVFQXXBNHHPLX-ZKWXMUAHSA-N Ala-Ala-His Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O WQVFQXXBNHHPLX-ZKWXMUAHSA-N 0.000 description 1
- GGNHBHYDMUDXQB-KBIXCLLPSA-N Ala-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)N GGNHBHYDMUDXQB-KBIXCLLPSA-N 0.000 description 1
- CLOMBHBBUKAUBP-LSJOCFKGSA-N Ala-Val-His Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N CLOMBHBBUKAUBP-LSJOCFKGSA-N 0.000 description 1
- 241000712892 Arenaviridae Species 0.000 description 1
- ULRPXVNMIIYDDJ-ACZMJKKPSA-N Asn-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)N)N ULRPXVNMIIYDDJ-ACZMJKKPSA-N 0.000 description 1
- RAUPFUCUDBQYHE-AVGNSLFASA-N Asn-Phe-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O RAUPFUCUDBQYHE-AVGNSLFASA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000776207 Bornaviridae Species 0.000 description 1
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 241001466953 Echovirus Species 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 208000000832 Equine Encephalomyelitis Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- 241000710781 Flaviviridae Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010061192 Haemorrhagic fever Diseases 0.000 description 1
- 241000150562 Hantaan orthohantavirus Species 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- FLYSHWAAHYNKRT-JYJNAYRXSA-N His-Gln-Phe Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O FLYSHWAAHYNKRT-JYJNAYRXSA-N 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 101001057750 Human cytomegalovirus (strain AD169) Uncharacterized protein IRL2 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- XMYURPUVJSKTMC-KBIXCLLPSA-N Ile-Ser-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N XMYURPUVJSKTMC-KBIXCLLPSA-N 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 241000701377 Iridoviridae Species 0.000 description 1
- 102100031413 L-dopachrome tautomerase Human genes 0.000 description 1
- 101710093778 L-dopachrome tautomerase Proteins 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 1
- 241000702259 Orbivirus Species 0.000 description 1
- 241000713112 Orthobunyavirus Species 0.000 description 1
- 241000712464 Orthomyxoviridae Species 0.000 description 1
- 241000150218 Orthonairovirus Species 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241000150350 Peribunyaviridae Species 0.000 description 1
- 241000713137 Phlebovirus Species 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 241000700625 Poxviridae Species 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 1
- 241000702247 Reoviridae Species 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 241000711931 Rhabdoviridae Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- HBTCFCHYALPXME-HTFCKZLJSA-N Ser-Ile-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HBTCFCHYALPXME-HTFCKZLJSA-N 0.000 description 1
- AZWNCEBQZXELEZ-FXQIFTODSA-N Ser-Pro-Ser Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O AZWNCEBQZXELEZ-FXQIFTODSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 241000710924 Togaviridae Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- KSVMDJJCYKIXTK-IGNZVWTISA-N Tyr-Ala-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 KSVMDJJCYKIXTK-IGNZVWTISA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 108700010877 adenoviridae proteins Proteins 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000011013 endotoxin removal Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000029570 hepatitis D virus infection Diseases 0.000 description 1
- 108010040030 histidinoalanine Proteins 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000019449 other food additives Nutrition 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241000724775 unclassified viruses Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/54—Proteins
- A23V2250/542—Animal Protein
- A23V2250/5434—Immunoglobulines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55516—Proteins; Peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
본 발명은 대장균 부착 단백질 FimH를 유효성분으로 포함하는 항암 면역 증강용 조성물에 관한 것으로서, 구체적으로, 본 발명의 FimH는 단백질 성분의 면역 증강제로 암 항원과 혼합 투여로 암치료 효과를 나타내며 면역관문억제제와 혼합 투여에도 암 치료 효율을 나타내어 암 치료용으로 사용시에 효과가 우수하다. 또한, 본 발명의 면역 증강제 FimH는 피하 투여 외에도 비강으로 투여하여 폐 면역을 활성화할 수 있고 폐암 항원과 혼합 투여로 폐암 치료에 효과가 우수하다. 또한, 본 발명의 면역 증강제 FimH는 동물 체내 면역 활성뿐만 아니라 사람의 말초 혈액의 수지상 세포와 T 림프구의 활성을 유도할 수 있다. 따라서, 본 발명의 FimH는 항암 치료시 면역 증강제로 유용하게 활용될 수 있다.The present invention relates to a composition for enhancing anti-cancer immunity comprising Escherichia coli attachment protein FimH as an active ingredient. It exhibits cancer treatment efficiency even when administered in combination with In addition, the immune enhancer FimH of the present invention can activate lung immunity by intranasal administration in addition to subcutaneous administration, and has excellent effects in lung cancer treatment when administered in combination with a lung cancer antigen. In addition, the immune enhancer FimH of the present invention can induce the activation of dendritic cells and T lymphocytes in human peripheral blood as well as immune activity in animals. Therefore, FimH of the present invention can be usefully used as an immune enhancer in anticancer treatment.
Description
본 발명은 대장균 부착 단백질 FimH를 유효성분으로 포함하는 항암 면역 증강용 조성물에 대한 것이다.The present invention relates to a composition for enhancing anticancer immunity comprising E. coli adhesion protein FimH as an active ingredient.
암세포는 정상세포에서 발생하여 무한 증식할 수 있는 능력을 가지고 있고 면역 세포의 공격으로부터 회피할 수 있는 능력까지 가지고 있다. 면역 세포가 암을 발견하더라도 암세포는 다양한 면역 억제 물질을 발현 및 분비하는 것으로 이 면역 세포로부터 공격을 회피하게 된다. 최근 연구 결과에 따르면 암세포 표면에 면역 관문 억제 단백질을 과발현하여 세포 독성 T 림프구로부터 공격을 회피하는 기능까지 확인되어 이를 중간에서 차단하는 방법이 암 치료제로 개발되고 있다. 이와 같이 면역 세포가 암세포를 병원성 세포로 인식할 수 있다면 암세포만을 선택적으로 사멸시킬 수 있다. 암을 치료하기 위한 면역요법으로 앞서 언급한 것과 같은 면역관문억제제를 이용한 방법과 암세포의 항원을 면역 증강제와 함께 투여하여 암 항원 특이적인 세포 독성 T 림프구를 증식시켜 암에 대한 치료 및 백신(cancer vaccine)으로 개발하는 방법이 일반적이다. 이를 위해서는 효과적이고 안정적인 면역 증강제가 필요하고 이러한 면역 증강제를 개발하기 위한 연구가 활발하게 진행되고 있다. Cancer cells arise from normal cells and have the ability to proliferate indefinitely and even have the ability to evade the attack of immune cells. Even if immune cells detect cancer, cancer cells evade attacks from these immune cells by expressing and secreting various immunosuppressive substances. According to recent research results, overexpression of immune checkpoint inhibitory proteins on the surface of cancer cells has confirmed the function of avoiding attacks from cytotoxic T lymphocytes, and a method of blocking them in the middle is being developed as a cancer treatment. In this way, if immune cells can recognize cancer cells as pathogenic cells, only cancer cells can be selectively killed. Immunotherapy for treating cancer is a method using immune checkpoint inhibitors as mentioned above and administering cancer cell antigens together with immune enhancers to proliferate cancer antigen-specific cytotoxic T lymphocytes for cancer treatment and vaccine (cancer vaccine). ) method is common. To this end, an effective and stable immune enhancer is required, and research to develop such an immune enhancer is being actively conducted.
면역 증강제는 우리 몸의 면역을 전반적으로 활성화시킬 수 있는 물질로 특히 항원 제시 세포(수지상 세포)의 활성을 유도하여 암 항원을 효율적으로 세포 표면에 표지해야 하고, 결과적으로 항원 특이적 helper T(Th) 세포 그리고 세포 독성 T 림프구(cytotoxic T lymphocytes; CTL)의 활성을 유도하여야 한다. 이렇게 활성화된 T 림프구들은 항원을 발현하는 암세포를 찾아 선택적으로 사멸하게 되고 암의 성장을 억제하게 된다. Immunity enhancers are substances that can activate the body's immunity in general, and in particular, induce the activity of antigen-presenting cells (dendritic cells) to efficiently label cancer antigens on the cell surface. As a result, antigen-specific helper T (Th ) cells and the activation of cytotoxic T lymphocytes (CTL). The activated T lymphocytes find cancer cells that express the antigen and selectively kill them, thereby suppressing cancer growth.
인류는 암 외에도 다양한 병원균의 감염으로 위협받고 있다. 이러한 감염 질환을 치료하고 방어하기 위해 감염 질환의 항원을 이용한 백신의 개발이 다양한 방법으로 진행되고 있으나 급속도로 변이하고 다양화되고 있는 병원균에 적절하게 대처하지 못하고 있다. 면역 증강제는 병원균의 항원과 혼합되어 백신으로 개발될 수도 있다.In addition to cancer, mankind is threatened by infection with various pathogens. In order to treat and defend these infectious diseases, the development of vaccines using antigens of infectious diseases is progressing in various ways, but they do not adequately cope with rapidly mutating and diversifying pathogens. Immunity enhancers can also be developed as vaccines by mixing with antigens of pathogens.
본 발명의 목적은 대장균 부착 단백질 FimH를 유효성분으로 포함하는 면역 증강제(adjuvant) 조성물을 제공하는 데에 있다.An object of the present invention is to provide an adjuvant composition comprising E. coli adhesion protein FimH as an active ingredient.
또한, 본 발명의 다른 목적은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 백신 조성물을 제공하는 데에 있다.Another object of the present invention is to provide a vaccine composition comprising E. coli attachment protein FimH and an antigen as active ingredients.
또한, 본 발명의 또 다른 목적은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 암 예방, 개선 또는 치료용 조성물을 제공하는 데에 있다.In addition, another object of the present invention is to provide a composition for preventing, improving or treating cancer comprising E. coli attachment protein FimH and an antigen as active ingredients.
또한, 본 발명의 또 다른 목적은 대장균 부착 단백질 FimH 및 항원을 피하 및 비강으로 투여가능한 암 예방, 개선 또는 치료용 조성물을 제공하는 데에 있다.Another object of the present invention is to provide a composition for preventing, ameliorating, or treating cancer capable of administering E. coli adhesion protein FimH and antigen subcutaneously or intranasally.
또한, 본 발명의 또 다른 목적은 대장균 부착 단백질 FimH 및 면역관문억제제를 유효성분으로 포함하는 암 예방, 개선 또는 치료용 조성물을 제공하는 데에 있다.In addition, another object of the present invention is to provide a composition for preventing, improving or treating cancer comprising E. coli attachment protein FimH and an immune checkpoint inhibitor as active ingredients.
상기 목적을 달성하기 위하여, 본 발명은 대장균 부착 단백질 FimH를 유효성분으로 포함하는 면역 증강제(adjuvant) 조성물을 제공한다.In order to achieve the above object, the present invention provides an adjuvant composition comprising E. coli adhesion protein FimH as an active ingredient.
또한, 본 발명은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 백신 조성물을 제공한다.In addition, the present invention provides a vaccine composition comprising E. coli attachment protein FimH and an antigen as active ingredients.
또한, 본 발명은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 암 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating cancer comprising E. coli adhesion protein FimH and an antigen as active ingredients.
또한, 본 발명은 대장균 부착 단백질 FimH 및 면역관문억제제를 유효성분으로 포함하는 암 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating cancer comprising E. coli adhesion protein FimH and an immune checkpoint inhibitor as active ingredients.
또한, 본 발명은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 암 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving cancer comprising E. coli attachment protein FimH and an antigen as active ingredients.
또한, 본 발명은 대장균 부착 단백질 FimH 및 면역관문억제제를 유효성분으로 포함하는 암 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving cancer, comprising E. coli attachment protein FimH and an immune checkpoint inhibitor as active ingredients.
본 발명은 대장균 부착 단백질 FimH를 유효성분으로 포함하는 항암 면역 증강용 조성물에 관한 것으로서, 구체적으로, 본 발명의 FimH는 단백질 성분의 면역 증강제로 암 항원과 혼합 투여로 암치료 효과를 나타내며 면역관문억제제와 혼합 투여에도 암 치료 효율을 나타내어 암 치료용으로 사용시에 효과가 우수하다. 또한, 본 발명의 면역 증강제 FimH는 피하 투여 외에도 비강으로 투여하여 폐 면역을 활성화할 수 있고 폐암 항원과 혼합 투여로 폐암 치료에 효과가 우수하다. 또한, 본 발명의 면역 증강제 FimH는 동물 체내 면역 활성뿐만 아니라 사람의 말초 혈액의 수지상 세포와 T 림프구의 활성을 유도할 수 있다. 따라서, 본 발명의 FimH는 항암 치료시 면역 증강제로 유용하게 활용될 수 있다.The present invention relates to a composition for enhancing anti-cancer immunity comprising Escherichia coli attachment protein FimH as an active ingredient. It exhibits cancer treatment efficiency even when administered in combination with In addition, the immune enhancer FimH of the present invention can activate lung immunity by intranasal administration in addition to subcutaneous administration, and has excellent effects in lung cancer treatment when administered in combination with a lung cancer antigen. In addition, the immune enhancer FimH of the present invention can induce the activation of dendritic cells and T lymphocytes in human peripheral blood as well as immune activity in animals. Therefore, FimH of the present invention can be usefully used as an immune enhancer in anticancer treatment.
도 1은 본 발명에서 사용된 면역 증강제 FimH를 대장균 및 효모에서 추출한 결과이다. (A) 대장균에 pET28a-FimH를 형질전환하고 니켈 컬럼을 이용하여 FimH를 추출한 결과이다. (B)는 pPIC9K-FimH를 이용하여 효모에 FimH를 과발현시키고 추출한 결과이다.
도 2는 FimH와 양성대조군인 내독소 (LPS)를 쥐 체내에 투여한 뒤 림프절 수지상 세포 아형의 활성을 확인한 것으로, (A)는 림프절 수지상 세포의 아형 분리를 보여주며, (B)는 CD8+와 CD8- 수지상 세포의 세포 표면 활성 단백질 인자의 발현 양상을 나타낸다.
도 3은 FimH와 내독소의 체내 염증 및 폐혈증 유발 비교 실험으로, (A)는 FimH의 농도에 따른 혈청에 분비된 염증성 사이토카인의 농도를 나타내며, (B)는 투여 농도에 따른 쥐 사멸을 나타낸다. (C)는 FimH와 내독소를 투여한 쥐의 폐 조직 사진을 보여준다.
도 4는 FimH가 유도하는 실험 항원 특이적 면역 활성 연구로, (A)는 실험 항원 OVA와 FimH의 혼합 투여에 따른 쥐 체내 OVA 특이적 T 림프구인 OT-I과 OT-II의 증식을 나타내며, (B)는 OVA를 발현하는 종양 내부로 침투한 OT-I과 OT-II 세포의 수를 나타낸다. (C, D 및 E)는 종양 침투 OT-I과 OT-II 세포의 세포 독성 사이토카인의 발현을 나타낸다.
도 5는 FimH와 암 항원의 혼합 투여에 따른 항암 효과를 확인한 결과로, (A 및 B)는 실험 항원인 OVA와 FimH를 혼합 투여하여 OVA를 발현하는 흑색종의 성장을 나타내고 암 투여 21일째의 종양 크기를 나타내며, (C 및 D)는 흰쥐에 상피세포암종을 이식하고 상피세포암종의 항원인 AH1A5와 FimH를 혼합 투여하여 암의 성장과 종양 크기를 확인한 결과이다. (E와 F)는 검은 쥐의 흑색종 성장과 종양의 크기를 나타낸다.
도 6은 FimH의 비강 투여에 의한 면역 활성 능력과 폐암 치료 결과를 나타내는 것으로, (A) 비강 투여 후 폐 림프절 수지상 세포의 활성을 나타내며, (B) FimH와 실험 항원 OVA의 혼합 투여에 따른 이식한 OT-I과 OT-II 세포의 증식을 폐 림프절에서 확인한 결과이다. (C)는 폐로 전이된 흑색종의 폐 사진과 흑색종 전이 수를 나타낸다.
도 7은 면역관문억제제인 항-PD-L1 항체와 FimH의 혼합 투여에 따른 항암 효과를 확인한 것으로, (A) 흰쥐의 상피세포암종의 성장을 확인한 결과이며, (B)는 암에 침투된 세포 독성 T 림프구의 독성 사이토카인의 발현을 나타낸다. (C 및 D)는 쥐의 치료 후 상피세포암종의 항원인 AH1A5에 대한 인터페론-감마의 발현 정도를 나타낸다.
도 8은 사람 말초 혈액의 수지상 세포와 T 림프구의 활성을 확인한 결과로서, (A)는 사람 수지상 세포의 분포를 유세포 분석기로 분석한 결과이며, (B)는 FimH와 양성대조군 내독소에 의한 사람 말초 혈액 수지상 세포의 활성을 확인한 결과이다. (C)는 활성화된 수지상 세포에 의한 자가 T 림프구의 증식 및 인터페론-감마의 발현을 확인한 결과이다.1 is a result of extracting the immune enhancer FimH used in the present invention from E. coli and yeast. (A) Results of transforming E. coli with pET28a-FimH and extracting FimH using a nickel column. (B) is the result of over-expression and extraction of FimH in yeast using pPIC9K-FimH.
Figure 2 confirms the activity of lymph node dendritic cell subtypes after administration of FimH and endotoxin (LPS), a positive control, into mice. (A) shows the subtype separation of lymph node dendritic cells, (B) shows CD8+ and Expression patterns of cell surface active protein factors of CD8- dendritic cells are shown.
Figure 3 is a comparison experiment of inducing inflammation and sepsis in the body of FimH and endotoxin, (A) shows the concentration of inflammatory cytokines secreted into serum according to the concentration of FimH, and (B) shows the death of mice according to the administered concentration. . (C) shows a photograph of the lung tissue of mice administered with FimH and endotoxin.
Figure 4 is an experimental antigen-specific immune activity study induced by FimH, (A) shows the proliferation of OVA-specific T lymphocytes, OT-I and OT-II, in mice according to the mixed administration of the experimental antigens OVA and FimH, (B) shows the number of OT-I and OT-II cells infiltrating OVA-expressing tumors. (C, D and E) show the expression of cytotoxic cytokines in tumor-infiltrating OT-I and OT-II cells.
Figure 5 is a result of confirming the anticancer effect according to the mixed administration of FimH and cancer antigen. (A and B) show the growth of OVA-expressing melanoma by the mixed administration of OVA and FimH, which are experimental antigens, on the 21st day of cancer administration. (C and D) show the tumor size, and (C and D) are the results of confirming the tumor growth and tumor size by transplanting epithelial cell carcinoma into rats and administering a mixture of AH1A5 and FimH, antigens of epithelial cell carcinoma. (E and F) show melanoma growth and tumor size in black mice.
Figure 6 shows the immune activation ability and lung cancer treatment results by nasal administration of FimH, (A) showing the activity of lung lymph node dendritic cells after nasal administration, (B) transplantation according to the mixed administration of FimH and experimental antigen OVA. This is the result of confirming the proliferation of OT-I and OT-II cells in lung lymph nodes. (C) shows lung photographs of metastasized melanoma to the lung and the number of melanoma metastases.
Figure 7 confirms the anticancer effect according to the mixed administration of anti-PD-L1 antibody and FimH, which are immune checkpoint inhibitors. Expression of toxic cytokines of toxic T lymphocytes. (C and D) show the expression level of interferon-gamma against AH1A5, an epithelial cell carcinoma antigen, after treatment in mice.
Figure 8 is a result of confirming the activity of dendritic cells and T lymphocytes in human peripheral blood, (A) is the result of analyzing the distribution of human dendritic cells by flow cytometry, and (B) is a human by FimH and positive control endotoxin. This is the result of confirming the activity of peripheral blood dendritic cells. (C) is the result of confirming the proliferation of autologous T lymphocytes and the expression of interferon-gamma by activated dendritic cells.
본 발명은 대장균 부착 단백질 FimH를 유효성분으로 포함하는 면역 증강제(adjuvant) 조성물을 제공한다.The present invention provides an adjuvant composition comprising E. coli adhesion protein FimH as an active ingredient.
바람직하게는, 상기 조성물은 말초 혈액 면역 세포의 활성을 유도할 수 있으나, 이에 제한되는 것은 아니다. 또한, 주변 림프절의 수지상 세포와 T 림프구의 활성을 유도할 수 있다.Preferably, the composition may induce activation of peripheral blood immune cells, but is not limited thereto. In addition, it can induce the activation of dendritic cells and T lymphocytes in peripheral lymph nodes.
삭제delete
또한, 본 발명은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 백신 조성물을 제공한다.In addition, the present invention provides a vaccine composition comprising E. coli attachment protein FimH and an antigen as active ingredients.
바람직하게는, 상기 항원은 세포, 바이러스, 단백질, 펩타이드, 핵산, 올리고뉴클레오티드, 탄수화물 및 지질로 구성된 군에서 선택된 어느 하나 이상일 수 있으나, 이에 제한되는 것은 아니다.Preferably, the antigen may be any one or more selected from the group consisting of cells, viruses, proteins, peptides, nucleic acids, oligonucleotides, carbohydrates and lipids, but is not limited thereto.
바람직하게는, 상기 백신은 항암 백신 또는 바이러스 백신일 수 있으나, 이에 제한되는 것은 아니다.Preferably, the vaccine may be an anti-cancer vaccine or a virus vaccine, but is not limited thereto.
본 발명의 백신 조성물은 제제화될 경우 통상적으로 사용되는 충진제, 증량제, 안정화제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제할 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수용성제, 현탁제, 유제, 동결건조제제가 포함된다. 비수용성제제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.When the vaccine composition of the present invention is formulated, it can be prepared using commonly used diluents or excipients such as fillers, extenders, stabilizers, binders, wetting agents, disintegrants, and surfactants. Formulations for parenteral administration include sterilized aqueous solutions, water-insoluble agents, suspensions, emulsions, and lyophilized preparations. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous preparations and suspensions.
본 발명의 백신 조성물은 근육내 주사, 피하 주사, 피내 주사, 복막내 주사, 비강 투여, 구강 투여, 경피 투여 또는 경구 투여될 수 있으며, 투여대상의 나이, 성별, 체중 등에 따라 투여량이 달라질 수 있고, 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서도 백신의 투여량이 증감될 수 있다.The vaccine composition of the present invention may be intramuscular injection, subcutaneous injection, intradermal injection, intraperitoneal injection, nasal administration, oral administration, transdermal administration, or oral administration, and the dosage may vary depending on the age, sex, weight, etc. of the subject to be administered. , The dose of the vaccine may be increased or decreased depending on the route of administration, the severity of the disease, gender, weight, age, etc.
본 발명의 조성물은 백신 효율을 향상시킬 수 있는 면역 증강제로 사용이 가능하고, 상기 감염 질환은 박테리아, 기생충, 진균류, 바이러스, 비로이드 및 프리온에 의해 초래되는 감염 질환일 수 있다. The composition of the present invention can be used as an immune enhancer capable of improving vaccine efficiency, and the infectious disease may be an infectious disease caused by bacteria, parasites, fungi, viruses, viroids, and prions.
특히, 바이러스는 장내바이러스, 로터바이러스, 아데노바이러스 및 간염 바이러스일 수 있고, 상기 바이러스 외에도 레트로바이러스과(예를 들어, HIV-I(또한 HTLV-III, LAV 또는 HTLV-III/LAV, 또는 HIV-III으로서도 언급됨)와 같은 인간 면역 결핍 바이러스; 및 HIV-LP와 같은 다른 분리물); 피코나바이러스과(Picornaviridae)(예를 들어, 폴리오 바이러스(polio virus), A형 간염 바이러스, 엔테로바이러스, 인간 콕사키바이러스(human Coxsackie virus), 리노바이러스(rhinovirus), 에코바이러스(echovirus)); 칼시바이러스과(Calciviridae)(예를 들어, 위장염의 원인이 되는 종); 토가바이러스과(Togaviridae)(예를 들어, 말 뇌염 바이러스(equine encephalitis virus), 풍진 바이러스(rubella virus)); 플라비비아러스과(Flaviviridae)(예를 들어, 뎅기 바이러스(dengue virus), 뇌염 바이러스(encephalitis virus), 황열 바이러스(yellow fever virus)); 코로나바이러스과(Coronaviridae)(예를 들어, 코로나바이러스(coronavirus)); 랍도바이러스과(Rhabdoviridae)(예를 들어, 수포성구내염바이러스(vesicular stomatitis virus), 광견병 바이러스(rabies virus)); 필로바이러스과(예를 들어, 에볼라 바이러스(ebola virus)); 파라믹소바이러스과(Paramyxoviridae)(예를 들어, 파라인플루엔자 바이러스(parainfluenza virus), 볼거리 바이러스(mumps virus), 홍역 바이러스(measles virus), 호흡기세포융합 바이러스(respiratory syncytial virus)); 오소믹소바이러스과(Orthomyxoviridae)(예를 들어, 인플루엔자 바이러스(influenza virus)); 부니아바이러스(Bunyaviridae)(예를 들어, 한탄 바이러스(Hantaan virus), 부니아 바이러스(bunya virus), 플레보바이러스(phlebovirus) 및 나이로 바이러스(Nairo virus)); 아레나바이러스과(출혈열 바이러스(hemorrhagic fever virus)); 레오바이러스과(Reoviridae)(예를 들어, 레오바이러스(reovirus), 오르비바이러스(orbivirus) 및 로타바이러스(rotavirus)); 보르나바이러스과(Bornaviridae); 헤파드나바이러스과(Hepadnaviridae)(B형 간염 바이러스(Hepatitis B virus)); 파보바이러스과(Parvoviridae)(파보바이러스(Parvoviridae)); 파포바바이러스과(Papovaviridae)(유두종 바이러스(papilloma virus), 폴리오마 바이러스(polyoma virus)); 아데노바이러스과(Adenoviridae)(대부분의 아데노바이러스(Adenovirus)); 헤르페스바이러스과(Herpesviridae)(단순 포진 바이러스(herpes simplex virus, HSV) 1 및 2, 수두 대상 포진 바이러스(varicella zoster virus), 사이토메갈로바이러스(cytomegalovirus, CMV), 헤르페스 바이러스(herpes virus); 폭스바이러스과(Poxviridae)(바리올라 바이러스(variola virus), 우두 바이러스(vaccinia virus). 폭스 바이러스(pox virus)); 및 이리도바이러스과(Iridoviridae)(예를 들어, 아프리카 돼지 콜레라 바이러스(African swine fever virus)); 및 미분류 바이러스들(예를 들어 델타 간염(delta hepatitis)(B형 간염의 결핍된 부수체(satellite)인 것으로 생각됨), C형 간염(Hepatitis C); 노워크(Norwalk) 및 관련 바이러스, 및 아스트로 바이러스(astro virus)의 제제)를 포함하지만, 이에 제한되지 않는다. In particular, the virus may be an enterovirus, a rotavirus, an adenovirus and a hepatitis virus, and in addition to the above viruses, a retroviral family (e.g., HIV-I (also HTLV-III, LAV or HTLV-III/LAV, or HIV-III human immunodeficiency virus (also referred to as); and other isolates such as HIV-LP); Picornaviridae (eg, polio virus, hepatitis A virus, enterovirus, human Coxsackie virus, rhinovirus, echovirus); Calciviridae (eg, species that cause gastroenteritis); Togaviridae (eg equine encephalitis virus, rubella virus); Flaviviridae (eg, dengue virus, encephalitis virus, yellow fever virus); Coronaviridae (eg coronavirus); Rhabdoviridae (eg vesicular stomatitis virus, rabies virus); filoviridae (eg, ebola virus); Paramyxoviridae (eg, parainfluenza virus, mumps virus, measles virus, respiratory syncytial virus); Orthomyxoviridae (eg influenza virus); Bunyaviridae (eg, Hantaan virus, bunya virus, phlebovirus and Nairo virus); Arenaviridae (hemorrhagic fever virus); Reoviridae (eg, reovirus, orbivirus and rotavirus); Bornaviridae; Hepadnaviridae (Hepatitis B virus); Parvoviridae (Parvoviridae); Papovaviridae (papilloma virus, polyoma virus); Adenoviridae (most Adenoviruses); Herpesviridae (herpes simplex virus (HSV) 1 and 2, varicella zoster virus, cytomegalovirus (CMV), herpes virus; Poxviridae ) (variola virus, vaccinia virus, pox virus); and Iridoviridae (eg African swine fever virus); and Unclassified Viruses (e.g. delta hepatitis (thought to be a deficient satellite of hepatitis B), hepatitis C; Norwalk and related viruses, and astroviruses ( preparations of astro virus)), but are not limited thereto.
또한, 본 발명은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 암 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating cancer comprising E. coli adhesion protein FimH and an antigen as active ingredients.
바람직하게는, 상기 항원은 세포, 바이러스, 단백질, 펩타이드, 핵산, 올리고뉴클레오티드, 탄수화물 및 지질로 구성된 군에서 선택된 어느 하나 이상일 수 있으나, 이에 제한되는 것은 아니다.Preferably, the antigen may be any one or more selected from the group consisting of cells, viruses, proteins, peptides, nucleic acids, oligonucleotides, carbohydrates and lipids, but is not limited thereto.
보다 바람직하게는, 상기 항원은 서열번호 1로 표시되는 오브알부민(ovalbumin, OVA) 펩타이드(SIINFEKL), 서열번호 2로 표시되는 OVA 펩타이드(ISQAVHAAHAEINEAGR), 서열번호 3으로 표시되는 흑색종 항원 TRP2 펩타이드(SVYDFFVWL) 또는 서열번호 4로 표시되는 상피세포암종 항원 AH1A5 펩타이드(SPSYAYHQF) 일 수 있으나, 이에 제한되는 것은 아니다.More preferably, the antigen is an ovalbumin (OVA) peptide (SIINFEKL) represented by SEQ ID NO: 1, an OVA peptide (ISQAVHAAHAEINEAGR) represented by SEQ ID NO: 2, a melanoma antigen TRP2 peptide represented by SEQ ID NO: 3 ( SVYDFFVWL) or epithelial cell carcinoma antigen AH1A5 peptide represented by SEQ ID NO: 4 (SPSYAYHQF), but is not limited thereto.
또한, 본 발명은 대장균 부착 단백질 FimH 및 면역관문억제제를 유효성분으로 포함하는 암 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating cancer comprising E. coli adhesion protein FimH and an immune checkpoint inhibitor as active ingredients.
바람직하게는, 상기 면역관문억제제는 항-PD-1 항체 또는 항-PD-L1 항체일 수 있으나, 이에 제한되는 것은 아니다.Preferably, the immune checkpoint inhibitor may be an anti-PD-1 antibody or an anti-PD-L1 antibody, but is not limited thereto.
바람직하게는, 상기 암은 방광암, 유방암, 결장암, 신장암, 간암, 폐암, 난소암, 전립선암, 췌장암, 위암, 경부암, 갑상선암, 편평세포암, 상피세포암, 피부암, 백혈병, 급성 림프성 백혈병, B-세포 림프종, T-세포 림프종, 호지킨스 림프종, 비-호지킨스 림프종, 모발상 세포 림프종, 버켓 림프종, 급성 및 만성 골수성 백혈병, 전골수구 백혈병, 섬유육종, 횡문근육종, 흑색종, 정상피종, 기형암종, 신경모세포종, 신경교종, 성상세포종, 신경아세포종, 신경초종, 골육종, 색소성 건피증, 각화극세포종, 정상피종, 갑상선 여포상암 및 기형 암종으로 구성된 군에서 선택된 어느 하나 이상일 수 있으나, 이에 제한되는 것은 아니다.Preferably, the cancer is bladder cancer, breast cancer, colon cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, pancreatic cancer, stomach cancer, cervical cancer, thyroid cancer, squamous cell cancer, epithelial cell cancer, skin cancer, leukemia, acute lymphocytic leukemia , B-cell lymphoma, T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy cell lymphoma, Burkett's lymphoma, acute and chronic myelogenous leukemia, promyelocytic leukemia, fibrosarcoma, rhabdomyosarcoma, melanoma, seminoma , teratocarcinoma, neuroblastoma, glioma, astrocytoma, neuroblastoma, schwannoma, osteosarcoma, xeroderma pigmentosum, keratoacanthoma, seminoma, thyroid follicular cancer and teratocarcinoma, but may be any one or more selected from the group consisting of, It is not limited.
바람직하게는, 상기 조성물은 근육내 주사, 피하 주사, 피내 주사, 복막내 주사, 비강 투여, 구강 투여, 경피 투여 또는 경구 투여될 수 있으나, 이에 제한되는 것은 아니다.Preferably, the composition may be intramuscular injection, subcutaneous injection, intradermal injection, intraperitoneal injection, nasal administration, oral administration, transdermal administration or oral administration, but is not limited thereto.
본 발명의 약학 조성물은 유효 성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등의 가용화제를 사용할 수 있다. 본 발명의 약학 조성물은 투여를 위해서 유효 성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1 종 이상 포함하여 약학 조성물로 바람직하게 제제화할 수 있다. 액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 완충 식염수, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한, 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 액제, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. The pharmaceutical composition of the present invention can be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, a disintegrant, a sweetener, a binder, a coating agent, an expanding agent, a lubricant, and a glidant. Alternatively, a solubilizer such as a flavoring agent may be used. The pharmaceutical composition of the present invention may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredient for administration. In compositions formulated as liquid solutions, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components. may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added if necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate solutions such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets.
본 발명의 약학 조성물의 유효성분의 유효량은 질환의 예방 또는 치료 요구되는 양을 의미한다. 따라서, 질환의 종류, 질환의 중증도, 조성물에 함유된 유효 성분 및 다른 성분의 종류 및 함량, 제형의 종류 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료 기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다.An effective amount of the active ingredient of the pharmaceutical composition of the present invention means an amount required for preventing or treating a disease. Therefore, the type of disease, the severity of the disease, the type and amount of the active ingredient and other ingredients contained in the composition, the type of formulation and the patient's age, weight, general health condition, sex and diet, administration time, administration route and composition It can be controlled by various factors including secretion rate, duration of treatment, and drugs used concurrently.
또한, 본 발명은 대장균 부착 단백질 FimH 및 항원을 유효성분으로 포함하는 암 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving cancer comprising E. coli attachment protein FimH and an antigen as active ingredients.
또한, 본 발명은 대장균 부착 단백질 FimH 및 면역관문억제제를 유효성분으로 포함하는 암 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving cancer, comprising E. coli attachment protein FimH and an immune checkpoint inhibitor as active ingredients.
본 발명의 건강기능식품 조성물은 분말, 과립, 정제, 캡슐, 시럽 또는 음료의 형태로 제공될 수 있으며, 상기 건강기능식품 조성물은 유효성분 이외에 다른 식품 또는 식품 첨가물과 함께 사용되고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 그의 사용 목적 예를 들어 예방, 건강 또는 치료적 처치에 따라 적합하게 결정될 수 있다.The health functional food composition of the present invention may be provided in the form of powder, granule, tablet, capsule, syrup or beverage, and the health functional food composition is used with other food or food additives in addition to the active ingredient, and according to a conventional method can be used appropriately. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use thereof, for example, prevention, health or therapeutic treatment.
상기 건강기능식품 조성물에 함유된 유효성분의 유효용량은 상기 약학조성물의 유효용량에 준해서 사용할 수 있으나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있으며, 유효성분은 안전성 면에서 아무런 문제가 없기 때문에 상기 범위 이상의 양으로도 사용될 수 있음은 확실하다.The effective dose of the active ingredient contained in the health functional food composition can be used according to the effective dose of the pharmaceutical composition, but in the case of long-term intake for the purpose of health and hygiene or health control, it is less than the above range. It is certain that the active ingredient can be used in an amount greater than the above range because there is no problem in terms of safety.
상기 건강식품의 종류에는 특별한 제한이 없고, 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등을 들 수 있다.There is no particular limitation on the type of health food, and examples include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, Drinks, alcoholic beverages, vitamin complexes, and the like are exemplified.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples will be described in detail to aid understanding of the present invention. However, the following examples are merely illustrative of the contents of the present invention, but the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.
<< 실시예Example 1> 대장균 및 효모에서 1> In Escherichia coli and yeast FimH의FimH's 추출 extraction
FimH를 대장균과 효모에서 대량 생산하기 위하여 대장균은 pET28a 플라스미드 백터를 사용하였고, 효모는 pPIC9K 백터를 사용하였다. 먼저, 대장균에 FimH를 분리하기 위해 Competent 세포에 pET28a-FimH 플라스미드를 형질전환한 후 37℃에서 배양한다. 180 rpm에서 LB 배지에 1시간 동안 배양한 후, 카나마이신(kanamycin)을 처리한 LB plate에 대장균을 다시 배양한다. 단일 콜로니를 확인하고 카나마이신 포함된 1 리터의 LB 배지에 단일 클론 대장균을 16시간 배양한다. 원심 분리 후 대장균을 분쇄하고 세포 부유액의 OD280 값이 기준치에 도달할 때까지 니켈 컬럼을 통과시킨다. 이어서 표적 FimH 단백질을 Ni-IDA wash buffer (8 M urea; 100 mM NaH2PO4; 100 mM Tris, pH 6.3)로 용리시키고 분리된 FimH를 수확한다.To mass-produce FimH in E. coli and yeast, the pET28a plasmid vector was used for E. coli and the pPIC9K vector was used for yeast. First, in order to isolate FimH from Escherichia coli, competent cells were transformed with the pET28a-FimH plasmid and then cultured at 37°C. After culturing for 1 hour in LB medium at 180 rpm, E. coli is cultured again on an LB plate treated with kanamycin. Confirm a single colony and incubate the monoclonal E. coli in 1 liter of LB medium containing kanamycin for 16 hours. After centrifugation, E. coli is pulverized and the cell suspension is passed through a nickel column until the OD280 value reaches the standard value. Then, the target FimH protein is eluted with Ni-IDA wash buffer (8 M urea; 100 mM NaH 2 PO 4 ; 100 mM Tris, pH 6.3), and the separated FimH is harvested.
효모로부터 FimH를 생산하기 위해서, 전장서열 스플라이싱 프라이머(full-length splicing primers)는 양쪽 말단에 보호 염기(protective bases)를 포함시켜 제작하였다. 합성 유전자 FimH를 EcoR I 및 Not I의 클로닝 부분을 발현벡터 pPIC9K에 삽입한다. 재조합 플라스미드 pPIC9K-FimH를 TOP10 클론 균주에 형질 전환한 후 배양하고 니컬 컬럼으로 분리한다. 대장균과 효모에서 분리된 FimH는 정제를 위해 14 kD의 투석 후 내독소 제거 레진을 이용하여 내독소의 오염을 제거하였다(도 1). To produce FimH from yeast, full-length splicing primers were prepared by including protective bases at both ends. The synthetic gene FimH, the cloning parts of EcoR I and Not I are inserted into the expression vector pPIC9K. The recombinant plasmid pPIC9K-FimH was transformed into a TOP10 clonal strain, cultured, and separated by a nick column. FimH isolated from Escherichia coli and yeast was purified by dialysis of 14 kD, and endotoxin contamination was removed using endotoxin removal resin (FIG. 1).
<< 실시예Example 2> 2> FimH의FimH's 피하 투여에 따른 림프절 수지상 세포의 활성 확인 Confirmation of activity of lymph node dendritic cells following subcutaneous administration
검은 쥐 피하에 2.5 mg/kg 농도의 FimH 및 1 mg/kg 농도의 LPS를 투여하고 24시간 뒤 전립선 림프절을 적출하고 수지상 세포의 활성을 분석하였다. 전립선 수지상 세포는 유세포 분석기를 이용하여 Lineage를 발현하지 않고 CD11c를 발현하는 살아있는 단일 부유 백혈구를 구획하였으며, 이를 CD8의 발현 유무에 따라 다시 아형으로 분리하였다. FimH를 투여하였던 쥐에서 수지상 세포 활성 표면 단백질 발현 인자의 발현이 각각의 아형에서 급격히 증가되는 것이 관찰되었고, 이 증가 정도는 양성대조군인 내독소 (LPS) 보다 높은 것으로 확인되었다(도 2). 2.5 mg/kg of FimH and 1 mg/kg of LPS were subcutaneously administered to black mice, and 24 hours later, prostate lymph nodes were removed and dendritic cell activity was analyzed. Prostate dendritic cells were divided into living single floating leukocytes expressing CD11c without expressing Lineage using flow cytometry, and these were further separated into subtypes according to the presence or absence of CD8 expression. It was observed that the expression of dendritic cell activity surface protein expression factor was rapidly increased in each subtype in mice administered with FimH, and the degree of increase was confirmed to be higher than that of endotoxin (LPS), a positive control group (FIG. 2).
<< 실시예Example 3> 내독소에 비해 현저히 낮은 체내 독성을 유발하는 3> Causes significantly less toxicity in the body than endotoxin FimHFimH
면역 증강제는 면역을 활성하는 것에 주안점을 두지만 체내의 독성을 유발할 경우 사용이 불가능하다. 이에 따라, FimH의 독성 정도를 확인하였을 때, FimH는 면역 활성 농도인 2.5 mg/kg보다 100배 높은 농도로 쥐에 투여하였을 때 전구 염증 사이토카인의 발현이 더 이상 증가 되지 않는 것을 확인하였다. 또한, 쥐 사멸 실험에서도 100배 높은 농도에서 30%의 쥐가 죽은 것에 비해 내독소는 20배 높은 농도로 투여하였을 때 36시간 내에 모든 쥐가 죽는 것으로 나타났으며, 폐의 염증에 있어서도 FimH는 염증이 거의 없는 것에 비해 내독소는 염증이 심하게 유발되는 것이 확인되었다(도 3). Immunity enhancers focus on activating the immune system, but cannot be used if they cause toxicity in the body. Accordingly, when confirming the degree of toxicity of FimH, when FimH was administered to mice at a
<< 실시예Example 4> 4> FimH와with FimH 실험 항원의 혼합 투여에 따른 항원 특이적 면역 활성 확인 Confirmation of antigen-specific immune activity according to mixed administration of test antigens
FimH의 면역 활성 능력을 검증하기 위하여, 먼저 실험 항원인 OVA에만 특이적으로 증식 및 활성을 가질 수 있는 OT-I과 OT-II 쥐에서 CD8과 CD4를 발현하는 림프구를 추출하고, 이를 OVA를 세포 표면에 발현하는 흑색종이 이식된 CD45.2를 발현하는 정상 쥐에 이식하였다. 이식 24시간 뒤 OVA와 FimH를 혼합 투여한 암 주변 림프절을 적출하고 OT-I과 OT-II 세포의 증식을 확인하였을 때, 높은 효율로 이들 세포의 증식을 유도하는 것을 확인할 수 있었다. 또한, 흑색종 내부에 침투된 OT-I과 OT-II 세포가 급격히 증가되는 것이 확인되었고, 이들 침투 OT-I과 OT-II 세포는 높은 효율로 인터페론-감마와 TNF-알파를 분비하는 것으로 확인되었다(도 4).In order to verify the ability of FimH to activate the immune system, first, lymphocytes expressing CD8 and CD4 were extracted from OT-I and OT-II mice, which can have specific proliferation and activity only to OVA, the test antigen, and OVA was used as the cell. It was transplanted into normal mice expressing CD45.2 transplanted with surface-expressing melanoma. 24 hours after transplantation, when OVA and FimH were mixedly administered to remove the lymph nodes around the cancer and confirm the proliferation of OT-I and OT-II cells, it was confirmed that the proliferation of these cells was induced with high efficiency. In addition, it was confirmed that OT-I and OT-II cells infiltrated into the melanoma were rapidly increased, and these infiltrated OT-I and OT-II cells secreted interferon-gamma and TNF-alpha with high efficiency was (FIG. 4).
<< 실시예Example 5> 5> FimH와with FimH 암 항원의 혼합 투여에 의한 항암 효과 Anticancer effect by mixed administration of cancer antigens
FimH와 항원의 혼합 투여에 의한 항암 효과를 확인하기 위하여, 먼저 실험 항원인 OVA와 FimH를 OVA를 발현하는 흑색종이 이식된 검은 쥐에 7일 간격으로 2회 주사하였다. OVA와 FimH를 혼합 투여한 쥐에서는 흑색종 성장이 대조군에 비해 현저히 억제되는 것이 확인되었다. 또한, 상피세포암종의 자가 항원인 AH1A5와 흑색종의 자가항원인 TRP2를 FimH와 혼합 투여한 쥐에서도 암 성장이 억제되는 것이 관찰되어 FimH가 암 자가 항원에 대한 면역 또한 증가 시켜 항암 효과를 유도할 수 있는 것을 확인하였다(도 5).In order to confirm the anticancer effect of the combined administration of FimH and antigen, OVA and FimH, the experimental antigens, were first injected twice at 7-day intervals into black mice transplanted with OVA-expressing melanoma. It was confirmed that melanoma growth was significantly inhibited in mice administered with OVA and FimH as compared to the control group. In addition, cancer growth was also inhibited in rats in which AH1A5, an autoantigen of epithelial cell carcinoma, and TRP2, an autoantigen of melanoma, were administered in combination with FimH. It was confirmed that it was possible (FIG. 5).
<< 실시예Example 6> 6> FimH의FimH's 비강 투여에 따른 점막 면역 증강 효과 Mucosal immune-enhancing effect by nasal administration
FimH를 검은 쥐의 비강으로 흡입시키고 24시간 뒤 페 림프절을 적출하여 수지상 세포의 활성을 관찰하였다. 피하 주사와 유사하게 FimH는 높은 효율로 폐 림프절 수지상 세포의 활성을 유도하는 것으로 나타났으며, OT-I과 OT-II 세포 이식 후 OVA와 FimH를 비강으로 투여하였을 때도 이들 세포의 증식을 매우 높게 유도하는 것이 확인되었다. 또한, 흑색종의 정맥 이식에 따른 폐 전이 모델 검은 쥐에서 TRL2와 FimH를 혼합 투여하였을 때 폐의 암 전이가 억제되는 것이 확인되었다(도 6).FimH was inhaled into the nasal cavity of black mice, and 24 hours later, the lung lymph nodes were removed and the activity of dendritic cells was observed. Similar to subcutaneous injection, FimH has been shown to induce the activity of lung lymph node dendritic cells with high efficiency, and intranasal administration of OVA and FimH after OT-I and OT-II cell transplantation also showed very high proliferation of these cells. It was confirmed that induction In addition, it was confirmed that cancer metastasis in the lung was inhibited when TRL2 and FimH were mixedly administered to black mice, a lung metastasis model following vein transplantation of melanoma (FIG. 6).
<< 실시예Example 7> 관문억제제인 항 PD-L1 항체와 7> checkpoint inhibitor anti-PD-L1 antibody and FimH의FimH's 혼합 투여에 따른 항암 효과 Anticancer effect according to mixed administration
최근 관문억제제인 항 PD-1과 항 PD-L1 항체가 암치료에 많이 사용되고 있으나, 이들 단백질의 발현이 낮은 환자에게서 효율이 떨어지는 경향이 있다. 이에 따라 FimH의 면역 증강 효과를 이용하여 항 PD-L1 항체와 FimH를 상피세포암종이 이식된 흰쥐에 혼합투여하여 암 성장을 확인하였다. FimH와 항 PD-L1 항체를 혼합 투여한 쥐에서는 상피세포암종의 성장이 억제되는 것이 관찰되었고, 종양 침투 세포 독성 T 림프구가 더 높은 농도의 인터페론-감마와 TNF-알파를 분비하는 것과 관찰되어 FimH가 항 PD-L1 항체의 항암효과를 향상 시킨다는 것을 알 수 있었다(도 7).Anti-PD-1 and anti-PD-L1 antibodies, which are checkpoint inhibitors, have recently been widely used in cancer treatment, but they tend to be less effective in patients with low expression of these proteins. Accordingly, by using the immune enhancing effect of FimH, anti-PD-L1 antibody and FimH were mixedly administered to rats transplanted with epithelial cell carcinoma, and cancer growth was confirmed. In mice treated with FimH and anti-PD-L1 antibody, the growth of epithelial cell carcinoma was suppressed, and tumor-infiltrating cytotoxic T lymphocytes secreted higher concentrations of interferon-gamma and TNF-alpha. It was found that improves the anticancer effect of the anti-PD-L1 antibody (FIG. 7).
<< 실시예Example 8> 8> FimH의FimH's 사람 말초 혈액 면역 세포 활성 능력 확인 Confirmation of human peripheral blood immune cell activation ability
FimH의 사람 면역 세포 활성 능력을 확인하기 위하여 사람의 말초 혈액에 있는 단핵세포를 분리하였고, FimH를 이 세포에 처리하여 24시간 배양하였다. 수지상 세포를 구획하기 위해 쥐와 유사한 방법으로 Lineage 와 CD11c를 이용하였으며, 말초 혈액 수지상 세포 아형인 BDCA1과 BDCA3으로 각각 분리하여 활성을 관찰하였다. FimH는 쥐 체내의 결과와 유사하게 사람 말초 혈액 수지상 세포 아형의 활성을 높은 효율로 유도하는 것이 확인되었으며 활성화된 수지상 세포는 자가 T 세포의 증식 및 인터페론-감마의 발현을 유도하는 것으로 확인되었다(도 8). In order to confirm the ability of FimH to activate human immune cells, mononuclear cells from human peripheral blood were isolated, treated with FimH, and cultured for 24 hours. To compartmentalize dendritic cells, Lineage and CD11c were used in a manner similar to that of mice, and activity was observed by separating into peripheral blood dendritic cell subtypes, BDCA1 and BDCA3, respectively. It was confirmed that FimH induces the activity of human peripheral blood dendritic cell subtypes with high efficiency, similar to the results in mice, and the activated dendritic cells induce the proliferation of autologous T cells and the expression of interferon-gamma (Fig. 8).
이상과 같이, 본 발명은 비록 한정된 실시예와 도면에 의해 설명되었으나, 본 발명은 이것에 의해 한정되지 않으며 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에 의해 본 발명의 기술 사상과 아래에 기재될 청구범위의 균등 범위 내에서 다양한 수정 및 변형이 가능함은 물론이다. As described above, although the present invention has been described by the limited embodiments and drawings, the present invention is not limited thereto, and the technical spirit of the present invention and the following by those skilled in the art to which the present invention belongs Of course, various modifications and variations are possible within the scope of equivalents of the claims to be set forth.
<110> Research Cooperation Foundation of Yeungnam University
Pukyong National University Industry-University Cooperation Foundation
THE ASAN FOUNDATION
University of Ulsan Foundation For Industry Cooperation
<120> Adjuvant composition for cancer immunotherapy comprising
Escherichia coli adhesion portion FimH
<130> ADP-2020-0110
<160> 4
<170> KopatentIn 2.0
<210> 1
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> OVA peptide
<400> 1
Ser Ile Ile Asn Phe Glu Lys Leu
1 5
<210> 2
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> OVA peptide
<400> 2
Ile Ser Gln Ala Val His Ala Ala His Ala Glu Ile Asn Glu Ala Gly
1 5 10 15
Arg
<210> 3
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> TRP2 peptide
<400> 3
Ser Val Tyr Asp Phe Phe Val Trp Leu
1 5
<210> 4
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> AH1A5 peptide
<400> 4
Ser Pro Ser Tyr Ala Tyr His Gln Phe
1 5
<110> Research Cooperation Foundation of Yeungnam University
Pukyong National University Industry-University Cooperation Foundation
THE ASAN FOUNDATION
University of Ulsan Foundation For Industry Cooperation
<120> Adjuvant composition for cancer immunotherapy comprising
Escherichia coli adhesion portion FimH
<130> ADP-2020-0110
<160> 4
<170> KopatentIn 2.0
<210> 1
<211> 8
<212> PRT
<213> artificial sequence
<220>
<223> OVA peptide
<400> 1
Ser Ile Ile Asn Phe
Claims (14)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020200048612A KR102474924B1 (en) | 2020-04-22 | 2020-04-22 | Adjuvant composition for cancer immunotherapy comprising Escherichia coli adhesion portion FimH |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020200048612A KR102474924B1 (en) | 2020-04-22 | 2020-04-22 | Adjuvant composition for cancer immunotherapy comprising Escherichia coli adhesion portion FimH |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20210130425A KR20210130425A (en) | 2021-11-01 |
| KR102474924B1 true KR102474924B1 (en) | 2022-12-06 |
Family
ID=78519268
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020200048612A KR102474924B1 (en) | 2020-04-22 | 2020-04-22 | Adjuvant composition for cancer immunotherapy comprising Escherichia coli adhesion portion FimH |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR102474924B1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019175147A1 (en) | 2018-03-12 | 2019-09-19 | Janssen Vaccines & Prevention B.V. | Vaccines against intra-abdominal infections |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR122019025365B1 (en) | 2012-11-29 | 2022-07-26 | Cornell University | USE OF A VETERINARY COMPOSITION |
-
2020
- 2020-04-22 KR KR1020200048612A patent/KR102474924B1/en active IP Right Grant
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019175147A1 (en) | 2018-03-12 | 2019-09-19 | Janssen Vaccines & Prevention B.V. | Vaccines against intra-abdominal infections |
Non-Patent Citations (1)
| Title |
|---|
| Molecular Therapy, 제18권, 제7호, 1379-1388면(published online: 2010.5.4.)* |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20210130425A (en) | 2021-11-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lam et al. | Safety and clinical usage of Newcastle disease virus in cancer therapy | |
| EP2019857B1 (en) | Cd40 agonist antibody/type1 interferon synergistic adjuvant combination, conjugates containing and use thereof as a therapeutic to enhance cellular immunity | |
| Chang et al. | Oral administration of an Enoki mushroom protein FVE activates innate and adaptive immunity and induces anti-tumor activity against murine hepatocellular carcinoma | |
| RU2746118C2 (en) | Composition for rna administration | |
| RU2448729C2 (en) | Compositions causing specific response of cytotoxic t-lymphocytes, including lymph-ablative compound and molecule which contains antigen sequences and is targeted at specialised antigen-presenting cells | |
| US20190216898A1 (en) | Interleukin Combination and Use Thereof | |
| US9238064B2 (en) | Allogeneic cancer cell-based immunotherapy | |
| US20080008716A1 (en) | Combined Pharmaceutical Composition Comprising an Anti-4-1BB Monoclonal Antibody and Chemotherapeutic Anti-Cancer Agent for Preventing and Treating Cancer Disease | |
| JP7239911B2 (en) | Therapeutic agents comprising oncolytic vaccinia virus and NK cells and their use for drugs for the treatment of tumors and/or cancers | |
| KR20180042284A (en) | Smallpox vaccine for use in cancer treatment | |
| CN107488235B (en) | A kind of preparation and application of new enhanced antigen joint polypeptid induction liver cancer-specific CTL cell | |
| WO2006010558A1 (en) | Tumor-homing cells engineered to produce tumor necrosis factor-related apoptosis-inducing ligand (trail) | |
| CN101252946A (en) | Methods for the rapid expansion of antigen specific T-cells | |
| AU2005314271B2 (en) | Alpha thymosin peptides as cancer vaccine adjuvants | |
| KR20200139738A (en) | Neoadjuvant cancer treatment | |
| JP2018522880A (en) | Compositions and methods for combination therapy with dengue virus and dendritic cells | |
| CN109200270B (en) | Combined medicine capable of improving therapeutic effect of polypeptide vaccine on HPV (human papilloma Virus) infected tumor and application thereof | |
| JP6698541B2 (en) | Medicament for use in a method of inducing or prolonging a cellular cytotoxic immune response | |
| CN106543287B (en) | Conformational epitope vaccines and uses | |
| KR102474924B1 (en) | Adjuvant composition for cancer immunotherapy comprising Escherichia coli adhesion portion FimH | |
| WO2017147894A1 (en) | Composition for enhancing capacity to kill abnormal cells and use thereof | |
| van den Boorn et al. | Nucleic acid adjuvants: toward an educated vaccine | |
| US20100285055A1 (en) | Activation of natural killer (NK) cells and methods of use | |
| KR102478043B1 (en) | Composition for delivering of antigen | |
| CN113117088B (en) | Use of inhibitors of calcium activated chloride channels in tumor immunotherapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AMND | Amendment | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| X091 | Application refused [patent] | ||
| AMND | Amendment | ||
| X701 | Decision to grant (after re-examination) | ||
| GRNT | Written decision to grant |