JP2017538754A - 抗原送達系 - Google Patents
抗原送達系 Download PDFInfo
- Publication number
- JP2017538754A JP2017538754A JP2017532946A JP2017532946A JP2017538754A JP 2017538754 A JP2017538754 A JP 2017538754A JP 2017532946 A JP2017532946 A JP 2017532946A JP 2017532946 A JP2017532946 A JP 2017532946A JP 2017538754 A JP2017538754 A JP 2017538754A
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- cells
- delivery system
- cancer
- class
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000427 antigen Substances 0.000 title claims abstract description 38
- 108091007433 antigens Proteins 0.000 title claims abstract description 38
- 102000036639 antigens Human genes 0.000 title claims abstract description 38
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 93
- 210000004027 cell Anatomy 0.000 claims abstract description 79
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 74
- 239000002502 liposome Substances 0.000 claims abstract description 67
- 201000011510 cancer Diseases 0.000 claims abstract description 39
- 230000008685 targeting Effects 0.000 claims abstract description 39
- 230000002163 immunogen Effects 0.000 claims abstract description 24
- 241000712079 Measles morbillivirus Species 0.000 claims abstract description 8
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 claims abstract description 4
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 4
- 230000028993 immune response Effects 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000008629 immune suppression Effects 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 32
- 238000011282 treatment Methods 0.000 description 31
- 230000004900 autophagic degradation Effects 0.000 description 16
- 230000028327 secretion Effects 0.000 description 16
- 102000016613 Autophagy-Related Protein 7 Human genes 0.000 description 12
- 108010092778 Autophagy-Related Protein 7 Proteins 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 108020004459 Small interfering RNA Proteins 0.000 description 10
- 210000001744 T-lymphocyte Anatomy 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 230000001419 dependent effect Effects 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- 108091054437 MHC class I family Proteins 0.000 description 7
- 201000005505 Measles Diseases 0.000 description 7
- 238000002619 cancer immunotherapy Methods 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 241000700605 Viruses Species 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 6
- 102000043129 MHC class I family Human genes 0.000 description 5
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- 210000000612 antigen-presenting cell Anatomy 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 238000009169 immunotherapy Methods 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 5
- 101150048357 Lamp1 gene Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 108010079723 Shiga Toxin Proteins 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000030741 antigen processing and presentation Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 108700012359 toxins Proteins 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 102000009016 Cholera Toxin Human genes 0.000 description 3
- 108010049048 Cholera Toxin Proteins 0.000 description 3
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000004961 autolysosome Anatomy 0.000 description 3
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 3
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 3
- 229960001076 chlorpromazine Drugs 0.000 description 3
- 230000008045 co-localization Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000012202 endocytosis Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102000005853 Clathrin Human genes 0.000 description 2
- 108010019874 Clathrin Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 210000004957 autophagosome Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229930193282 clathrin Natural products 0.000 description 2
- 230000006395 clathrin-mediated endocytosis Effects 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 238000011198 co-culture assay Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 210000003712 lysosome Anatomy 0.000 description 2
- 230000001868 lysosomic effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 229960000988 nystatin Drugs 0.000 description 2
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 231100000654 protein toxin Toxicity 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 2
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 2
- LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical class CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 101001023095 Anemonia sulcata Delta-actitoxin-Avd1a Proteins 0.000 description 1
- 101000641989 Araneus ventricosus Kunitz-type U1-aranetoxin-Av1a Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101001028691 Carybdea rastonii Toxin CrTX-A Proteins 0.000 description 1
- 101000685083 Centruroides infamatus Beta-toxin Cii1 Proteins 0.000 description 1
- 101000685085 Centruroides noxius Toxin Cn1 Proteins 0.000 description 1
- 101001028688 Chironex fleckeri Toxin CfTX-1 Proteins 0.000 description 1
- 101000644407 Cyriopagopus schmidti U6-theraphotoxin-Hs1a Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 1
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000012270 PD-1 inhibitor Substances 0.000 description 1
- 239000012668 PD-1-inhibitor Substances 0.000 description 1
- 101000679608 Phaeosphaeria nodorum (strain SN15 / ATCC MYA-4574 / FGSC 10173) Cysteine rich necrotrophic effector Tox1 Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000007154 intracellular accumulation Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007056 liver toxicity Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000013178 mathematical model Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940121655 pd-1 inhibitor Drugs 0.000 description 1
- 229960002621 pembrolizumab Drugs 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007441 retrograde transport Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000012772 sequence design Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000000107 tumor biomarker Substances 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
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
- A61K39/12—Viral antigens
- A61K39/275—Poxviridae, e.g. avipoxvirus
- A61K39/285—Vaccinia virus or variola virus
-
- 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
- A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
- A61K39/165—Mumps or measles virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- 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
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
-
- 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
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/605—MHC molecules or ligands thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
- C12N2710/24134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18411—Morbillivirus, e.g. Measles virus, canine distemper
- C12N2760/18434—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Virology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Dispersion Chemistry (AREA)
- Mycology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
本発明は、癌細胞において特異的に免疫原性麻疹抗原の提示を促進するナノ粒子送達系を提供する。該送達系はウイルス粒子、毒素または生物学的に誘導された物質を含有しない。この系での治療は癌細胞に対する二次免疫応答の活性化を促進して、腫瘍関連抗原を特定する必要性または一次免疫応答により免疫系を教育する必要性を回避する。該送達系は、外部表面上に癌特異的標的化ペプチドを提示し免疫原性ヒト白血病抗原クラスI拘束性ペプチドを封入したステルスリポソームのみを要する三部構成モジュールビヒクルである。この標的化ナノ粒子は主要組織適合複合体クラスI分子における該ペプチドの提示を促進する。活性化は標的化ペプチド、過去の抗原曝露に左右され、新規オートファジー媒介性メカニズムを利用する。このリポソームでの処理(治療)は、ワクチン接種されたC57BL/6マウスにおける高悪性度LLC1モデルを使用した場合の腫瘍成長の有意な低減をもたらす。本発明者らは、スケーラブルであり、生物学的に誘導された物質を含有せず、有効な癌療法である新規細胞性免疫療法の原理証明を示す。
この原理証明研究において、本発明者らは、麻疹ヘマグルチニンタンパク質から特定された免疫原性HLAクラス1拘束性ペプチドであるH250(1)を封入したリポソームを合成した。該リポソームは、標的化ペプチドH1299.3を外部表面上に提示することにより(10)、癌細胞において特異的にインターナリゼーションされるように設計される。H1299.3は、エンドサイトーシスの明白なメカニズムにより癌細胞において優先的にインターナリゼーションされる癌特異的標的化ペプチドの選択を可能にする新規ファージ提示技術を用いて特定された20マーの癌特異的標的化ペプチドである。このペプチドをリジンコア上で二量体化した。それはファージ粒子の環境の外部において完全に機能的である。H1299.3ペプチドは、エンドサイトーシスのクラスリン依存的メカニズムにより、正常気管支上皮細胞対照細胞系と比較して非小細胞肺癌(NSCLC)細胞系のパネルにおいて特異的に蓄積する。この研究において、本発明者らは、CD8+特異的インターフェロン(IFN)γ分泌により示されるとおり、H1299.3が主要組織適合複合体(MHC)およびHLAクラスI分子の両方における免疫原性抗原の機能的提示を促進することを示している。また、H1299.3により促進される提示はオートファジー依存的メカニズムを利用している。最後に、H250を含有するH1299.3標的化リポソームでの処理は、ビヒクル対照での処理と比較して、ワクチン接種C57BL/6マウスに移植された皮下LLC1腫瘍の成長速度を実質的に低下させる。
1.Ota,MO,Ndhlovu,Z,Oh,S,Piyasirisilp,S,Berzofsky,JA,Moss,WJら(2007).Hemagglutinin protein is a primary target of the measles virus−specific HLA−A2− restricted CD8+ T cell response during measles and after vaccination.J Infect Dis 195:1799−1807.
2.Mellman,I,Coukos,GおよびDranoff,G(2011).Cancer immunotherapy comes of age.Nature 480:480−489.
3.Vitale,M,Cantoni,C,Pietra,G,Mingari,MCおよびMoretta,L(2014).Effect of tumor cells and tumor microenvironment on NK−cell function.Eur J Immunol 44:1582−1592.
4.Shiao,SL,Ganesan,AP,Rugo,HSおよびCoussens,LM(2011).Immune microenvironments in solid tumors:new targets for therapy.Genes Dev 25:2559−2572.
5.Chiocca,EAおよびRabkin,SD(2014).Oncolytic viruses and their application to cancer immunotherapy.Cancer Immunol Res 2:295−300.
6.Dudley,ME,Wunderlich,JR,Robbins,PF,Yang,JC,Hwu,P,Schwartzentruber,DJら(2002).Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes.Science 298:850−854.
7.Hamid,O,Robert,C,Daud,A,Hodi,FS,Hwu,WJ,Kefford,Rら(2013).Safety and tumor responses with lambrolizumab(anti−PD−1)in melanoma.N Engl J Med 369:134−144.
8.Guillerme,JB,Boisgerault,N,Roulois,D,Menager,J,Combredet,C,Tangy,Fら(2013).Measles virus vaccine−infected tumor cells induce tumor antigen cross−presentation by human plasmacytoid dendritic cells.Clin Cancer Res 19:1147−1158.
9.Dass,CR(2008).Drug delivery in cancer using liposomes.Methods Mol Biol 437:177−182.
10.Umlauf,BJ,Mercedes,JS,Chung,CYおよびBrown,KC(2014).Identification of a novel lysosomal trafficking peptide using phage display biopanning coupled with endocytic selection pressure.Bioconjug Chem 25:1829−1837.
11.van Endert,PM(1996).Peptide selection for presentation by HLA class I:a role for the human transporter associated with antigen processing? Immunol Res 15:265−279.
12.Gray,BP,McGuire,MJおよびBrown,KC(2013).A liposomal drug platform overrides peptide ligand targeting to a cancer biomarker,irrespective of ligand affinity or density.PLoS One 8:e72938.
13.Taurin,S,Nehoff,HおよびGreish,K(2012).Anticancer nanomedicine and tumor vascular permeability;Where is the missing link? J Control Release 164:265−275.
14.McGuire,MJ,Gray,BP,Li,S,Cupka,D,Byers,LA,Wu,Lら(2014).Identification and characterization of a suite of tumor targeting peptides for non−small cell lung cancer.Sci Rep 4:4480.
15.Klionsky,DJ(2007).Autophagy:from phenomenology to molecular understanding in less than a decade.Nat Rev Mol Cell Biol 8:931−937.
16.Shah,JK,Garner,HR,White,MA,Shames,DSおよびMinna,JD(2007).sIR:siRNA Information Resource,a web−based tool for siRNA sequence design and analysis and an open access siRNA database.BMC Bioinformatics 8:178.
17.Lee,RS,Tartour,E,van der Bruggen,P,Vantomme,V,Joyeux,I,Goud,Bら(1998).Major histocompatibility complex class I presentation of exogenous soluble tumor antigen fused to the B−fragment of Shiga toxin.Eur J Immunol 28:2726−2737.
18.Noakes,KL,Teisserenc,HT,Lord,JM,Dunbar,PR,Cerundolo,VおよびRoberts,LM(1999).Exploiting retrograde transport of Shiga−like toxin 1 for the delivery of exogenous antigens into the MHC class I presentation pathway.FEBS Lett 453:95−99.
19.Haicheur,N,Bismuth,E,Bosset,S,Adotevi,O,Warnier,G,Lacabanne,Vら(2000).The B subunit of Shiga toxin fused to a tumor antigen elicits CTL and targets dendritic cells to allow MHC class I−restricted presentation of peptides derived from exogenous antigens.J Immunol 165:3301−3308.
20.Sandvig,K,Spilsberg,B,Lauvrak,SU,Torgersen,ML,Iversen,TGおよびvan Deurs,B(2004).Pathways followed by protein toxins into cells.Int J Med Microbiol 293:483−490.
21.Johannes,LおよびRomer,W(2010).Shiga toxins−from cell biology to biomedical applications.Nat Rev Microbiol 8:105−116.
22.McEnaney,PJ,Parker,CG,Zhang,AXおよびSpiegel,DA(2012).Antibody−recruiting molecules:an emerging paradigm for engaging immune function in treating human disease.ACS Chem Biol 7:1139−1151.
23.Lu,YおよびLow,PS(2002).Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors.Cancer Immunol Immunother 51:153−162.
24.Crotzer,VLおよびBlum,JS(2009).Autophagy and its role in MHC−mediated antigen presentation.J Immunol 182:3335−3341.
25.Patterson,NLおよびMintern,JD(2012).Intersection of autophagy with pathways of antigen presentation.Protein Cell 3:911−920.
26.Nixon,RA(2013).The role of autophagy in neurodegenerative disease.Nat Med 19:983−997.
27.Sandvig,Kおよびvan Deurs,B(2002).Membrane traffic exploited by protein toxins.Annu Rev Cell Dev Biol 18:1−24.
28.Ovsyannikova,IG,Johnson,KL,Bergen,HR 3rdおよびPoland,GA(2007).Mass spectrometry and peptide−based vaccine development.Clin Pharmacol Ther 82:644−652.
29.Centers for Disease Control and Prevention(CDC)(2012).Vaccination coverage among children in kindergarten−−United States,2011−12 school year.MMWR Morb Mortal Wkly Rep 61:647−652.
30.Bauzon,MおよびHermiston,T(2014).Armed therapeutic viruses−a disruptive therapy on the horizon of cancer immunotherapy.Front Immunol 5:74.
31.Schwendener,RA,Ludewig,B,Cerny,AおよびEngler,O(2010).Liposome−based vaccines.Methods Mol Biol 605:163−175.
32.Umlauf,BJ,Pinsky,NA,Ovsyannikova,IGおよびPoland,GA(2012).Detection of vaccinia virus−specific IFNγ and IL−10 secretion from human PBMCs and CD8+ T cells by ELISPOT.Methods Mol Biol 792:199−218.
33.Fernandez−Vina,MA,Falco,M,Sun,YおよびStastny,P(1992).DNA typing for HLA class I alleles:I.Subsets of HLA−A2 and of −A28.Hum Immunol 33:163−173.
34.Chung,CY,Madhunapantula,SV,Desai,D,Amin,SおよびRobertson,GP(2011).Melanoma prevention using topical PBISe.Cancer Prev Res(Phila) 4:935−948.
35.Feldman,JP,Goldwasser,RおよびMark,S(2009).A mathematical model for tumor volume evaluation using two−dimensions.J Appl Quant 4:455−462.
本発明は、列挙される特定の及び好ましい実施形態の全ての組合せを含む。本明細書に記載されている実施例(具体例)および実施形態は例示を目的としたものであるに過ぎず、それを考慮して、種々の修飾または変更が当業者に示唆され、本出願の精神および範囲ならびに添付の特許請求の範囲の範囲内に含まれるべきであると理解される。本出願において引用されている全ての刊行物、特許および特許出願(それらにおける引用を含む)の全体を、あらゆる目的で、参照により本明細書に組み込まれることとする。
Claims (8)
- PEG化ステルスリポソームから実質的になる最小抗原送達系であって、
該リポソームは免疫原性ヒト白血球抗原(HLA)クラス拘束性ペプチドでローディングされており、且つ、標的細胞への該リポソームの結合およびインターナリゼーションを媒介する細胞標的化ペプチドで表面修飾されている、最小抗原送達系。 - 前記HLAクラス1拘束性ペプチドが、麻疹ウイルスヘマグルチニンペプチドH250である、請求項1記載の系。
- 前記細胞標的化ペプチドが、H1299.3である癌細胞標的化ペプチドである、請求項1記載の系。
- 前記HLAクラス1拘束性ペプチドが、麻疹ウイルスヘマグルチニンペプチドH250であり、
前記細胞標的化ペプチドが、H1299.3である癌細胞標的化ペプチドである、請求項1記載の系。 - HLAクラス拘束性ペプチドでローディングされたPEG化ステルスリポソームを、その表面に細胞標的化ペプチドを結合させることにより表面修飾する工程を含む、請求項1記載の抗原送達系の製造方法。
- 前記PEG化ステルスリポソームを、クラス拘束性ペプチドの存在下で該リポソームを形成させることによりローディングする工程、および、
前記HLAクラス拘束性ペプチドでローディングされたPEG化ステルスリポソームを、その表面に細胞標的化ペプチドを結合させることにより表面修飾する工程
を含む、請求項1記載の抗原送達系の製造方法。 - 前記抗原送達系を、それを要する宿主内に導入する工程を含む、請求項1記載の抗原送達系の使用方法。
- 前記抗原送達系を、それを要する宿主内に導入する工程、および
生じた免疫応答または標的細胞の抑制を検出する工程
を含む、請求項1記載の抗原送達系の使用方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462093285P | 2014-12-17 | 2014-12-17 | |
US62/093,285 | 2014-12-17 | ||
PCT/US2015/066519 WO2016100748A1 (en) | 2014-12-17 | 2015-12-17 | Antigen delivery system |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017538754A true JP2017538754A (ja) | 2017-12-28 |
JP6832278B2 JP6832278B2 (ja) | 2021-02-24 |
Family
ID=56127645
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017532946A Active JP6832278B2 (ja) | 2014-12-17 | 2015-12-17 | 抗原送達系 |
Country Status (9)
Country | Link |
---|---|
US (1) | US10925960B2 (ja) |
EP (1) | EP3226840B1 (ja) |
JP (1) | JP6832278B2 (ja) |
KR (1) | KR20170093970A (ja) |
CN (1) | CN107223051B (ja) |
AU (1) | AU2015364447B2 (ja) |
CA (1) | CA2971408C (ja) |
IL (1) | IL252972A0 (ja) |
WO (1) | WO2016100748A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10925960B2 (en) | 2014-12-17 | 2021-02-23 | Sri International | Antigen delivery system |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2019362400A1 (en) * | 2018-10-19 | 2021-04-22 | ETH Zürich | Chimeric molecules |
GB201919316D0 (en) * | 2019-12-24 | 2020-02-05 | Queens Univ Of Belfast | Polymeric nanoparticles for enhanced cancer treatment |
EP4199907A1 (en) * | 2020-09-21 | 2023-06-28 | SRI International | Targeted antigen delivery system and uses thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008105174A1 (ja) * | 2007-02-28 | 2008-09-04 | National University Corporation Hokkaido University | 細胞性免疫誘導用リポソーム |
US20130164364A1 (en) * | 2010-07-31 | 2013-06-27 | James C. Paulson | Liposome targeting compounds and related uses |
JP2014519496A (ja) * | 2011-05-11 | 2014-08-14 | ナノヴァレント ファーマシューティカルズ,インコーポレイテッド | Alcam細胞表面受容体を標的とする細胞毒性重合リポソームナノ粒子による増強された骨肉腫の増殖抑制 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998033520A1 (en) * | 1997-02-05 | 1998-08-06 | Bystryn Jean Claude | pH-SENSITIVE LIPOSOMES AND OTHER TYPES OF ENCAPSULATED VACCINES CONTAINING IMMUNOMODULATORS, AND METHODS FOR MAKING AND USING SAME |
EP2215111B1 (en) * | 2007-11-01 | 2016-03-16 | Mayo Foundation For Medical Education And Research | Hla-dr binding peptides and their uses |
BR112012023501A2 (pt) | 2010-03-19 | 2016-05-31 | Massachusetts Inst Technology | vesículas lipídicas multilamelares, composição farmacêutica e método |
US10272041B2 (en) * | 2013-03-15 | 2019-04-30 | The Penn State Research Foundation | Acid stable liposomal compositions and methods for producing the same |
FR3027748B1 (fr) | 2014-10-27 | 2016-11-04 | Valeo Equip Electr Moteur | Procede et dispositif de commande d'une machine electrique tournante synchrone polyphasee, et machine electrique reversible de vehicule automobile correspondant |
CN107223051B (zh) | 2014-12-17 | 2021-09-03 | 斯坦福国际研究院 | 抗原递送系统 |
-
2015
- 2015-12-17 CN CN201580075499.5A patent/CN107223051B/zh active Active
- 2015-12-17 JP JP2017532946A patent/JP6832278B2/ja active Active
- 2015-12-17 KR KR1020177019331A patent/KR20170093970A/ko unknown
- 2015-12-17 AU AU2015364447A patent/AU2015364447B2/en active Active
- 2015-12-17 WO PCT/US2015/066519 patent/WO2016100748A1/en active Application Filing
- 2015-12-17 EP EP15871129.1A patent/EP3226840B1/en active Active
- 2015-12-17 CA CA2971408A patent/CA2971408C/en active Active
-
2017
- 2017-06-17 US US15/626,075 patent/US10925960B2/en active Active
- 2017-06-18 IL IL252972A patent/IL252972A0/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008105174A1 (ja) * | 2007-02-28 | 2008-09-04 | National University Corporation Hokkaido University | 細胞性免疫誘導用リポソーム |
US20130164364A1 (en) * | 2010-07-31 | 2013-06-27 | James C. Paulson | Liposome targeting compounds and related uses |
JP2014519496A (ja) * | 2011-05-11 | 2014-08-14 | ナノヴァレント ファーマシューティカルズ,インコーポレイテッド | Alcam細胞表面受容体を標的とする細胞毒性重合リポソームナノ粒子による増強された骨肉腫の増殖抑制 |
Non-Patent Citations (2)
Title |
---|
BIOCONJUGATE CHEM., 2014, VOL.25, P.1829-1837, JPN6019038297, ISSN: 0004264210 * |
THE JOURNAL OF INFECTIOUS DISEASES, 2007, VOL.195, P.1799-1807, JPN6019038296, ISSN: 0004264209 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10925960B2 (en) | 2014-12-17 | 2021-02-23 | Sri International | Antigen delivery system |
Also Published As
Publication number | Publication date |
---|---|
IL252972A0 (en) | 2017-08-31 |
US10925960B2 (en) | 2021-02-23 |
EP3226840A4 (en) | 2017-12-13 |
EP3226840B1 (en) | 2020-07-29 |
CA2971408A1 (en) | 2016-06-23 |
JP6832278B2 (ja) | 2021-02-24 |
EP3226840A1 (en) | 2017-10-11 |
US20170281752A1 (en) | 2017-10-05 |
KR20170093970A (ko) | 2017-08-16 |
CN107223051B (zh) | 2021-09-03 |
CA2971408C (en) | 2019-12-10 |
AU2015364447B2 (en) | 2021-04-01 |
WO2016100748A1 (en) | 2016-06-23 |
AU2015364447A1 (en) | 2017-07-13 |
CN107223051A (zh) | 2017-09-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Gong et al. | Proton-driven transformable nanovaccine for cancer immunotherapy | |
Sun et al. | Nanomedicine and macroscale materials in immuno-oncology | |
Conniot et al. | Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators | |
Dong et al. | A visible codelivery nanovaccine of antigen and adjuvant with self-carrier for cancer immunotherapy | |
Cruz et al. | Targeting nanosystems to human DCs via Fc receptor as an effective strategy to deliver antigen for immunotherapy | |
Li et al. | Black phosphorous nanosheet: a novel immune-potentiating nanoadjuvant for near-infrared-improved immunotherapy | |
US11554097B2 (en) | Recombinant production of hybrid lipid-biopolymer materials that self-assemble and encapsulate agents | |
Avila et al. | Gene delivery and immunomodulatory effects of plasmid DNA associated with Branched Amphiphilic Peptide Capsules | |
US10925960B2 (en) | Antigen delivery system | |
RO119344B1 (ro) | Compoziţie farmaceutică pe bază de peptide şi adjuvanţi cu efect imunomodulator | |
US20240033335A1 (en) | Antigenic peptides for prevention and treatment of b-cell malignancy | |
Zhang et al. | Impact of dose, route, and composition on the immunogenicity of immune polyelectrolyte multilayers delivered on gold templates | |
Teplensky et al. | Spherical nucleic acid vaccine structure markedly influences adaptive immune responses of clinically utilized prostate cancer targets | |
Lee et al. | Virus-mimetic polymer nanoparticles displaying hemagglutinin as an adjuvant-free influenza vaccine | |
CN113557035A (zh) | 自组装肽纳米颗粒和其用途 | |
JP2023029997A (ja) | エンベロープウイルスの非遺伝的改変 | |
Blom et al. | Virosome-bound antigen enhances DC-dependent specific CD4+ T cell stimulation, inducing a Th1 and Treg profile in vitro | |
Li et al. | A" trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice | |
Zhao et al. | A co-formulated vaccine of irradiated cancer cells and cowpea mosaic virus improves ovarian cancer rejection | |
Li et al. | Cell membrane adhesive n-hexadecyl choline phosphate as vaccine delivery systems for anticancer immunotherapy | |
Berti et al. | Reduction-Sensitive Protein Nanogels Enhance Uptake of Model and Tumor Lysate Antigens In Vitro by Mouse-and Human-Derived Dendritic Cells | |
US20220127317A1 (en) | Antitumor cell comprising a charge modified globin | |
Umlauf et al. | Modular three-component delivery system facilitates HLA class I antigen presentation and CD8+ T-cell activation against tumors | |
Tohumeken et al. | A modular antigen presenting peptide/oligonucleotide nanostructure platform for inducing potent immune response | |
Cooney et al. | Synthesis and Biological Evaluation of Peptide-Adjuvant Conjugate Vaccines with Increasing Antigen Content |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181107 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190930 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191008 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200106 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200331 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200519 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200813 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201117 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210112 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210201 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6832278 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |