JP5563472B2 - 免疫学的効果を増大させる方法 - Google Patents
免疫学的効果を増大させる方法 Download PDFInfo
- Publication number
- JP5563472B2 JP5563472B2 JP2010536148A JP2010536148A JP5563472B2 JP 5563472 B2 JP5563472 B2 JP 5563472B2 JP 2010536148 A JP2010536148 A JP 2010536148A JP 2010536148 A JP2010536148 A JP 2010536148A JP 5563472 B2 JP5563472 B2 JP 5563472B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- irx
- tumor
- immune
- cell
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title description 50
- 230000001965 increasing effect Effects 0.000 title description 33
- 230000001900 immune effect Effects 0.000 title description 11
- 210000004027 cell Anatomy 0.000 claims description 256
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 212
- 230000006907 apoptotic process Effects 0.000 claims description 137
- 108010002350 Interleukin-2 Proteins 0.000 claims description 22
- 102000000588 Interleukin-2 Human genes 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 21
- 230000001681 protective effect Effects 0.000 claims description 18
- 239000008280 blood Substances 0.000 claims description 17
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 16
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 16
- 210000004369 blood Anatomy 0.000 claims description 16
- 108010074328 Interferon-gamma Proteins 0.000 claims description 8
- 108090001005 Interleukin-6 Proteins 0.000 claims description 7
- 102000004889 Interleukin-6 Human genes 0.000 claims description 7
- 108090001007 Interleukin-8 Proteins 0.000 claims description 7
- 102000004890 Interleukin-8 Human genes 0.000 claims description 7
- 108010047620 Phytohemagglutinins Proteins 0.000 claims description 7
- 229940100601 interleukin-6 Drugs 0.000 claims description 7
- 229940096397 interleukin-8 Drugs 0.000 claims description 7
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 claims description 7
- 230000001885 phytohemagglutinin Effects 0.000 claims description 7
- 102100037850 Interferon gamma Human genes 0.000 claims description 6
- 239000003226 mitogen Substances 0.000 claims description 6
- 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 claims description 5
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 5
- 230000002085 persistent effect Effects 0.000 claims description 5
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 3
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 3
- 238000011275 oncology therapy Methods 0.000 claims description 3
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 claims description 2
- 102000008070 Interferon-gamma Human genes 0.000 claims description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 claims description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 229940044627 gamma-interferon Drugs 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
- 108010043766 IRX 2 Proteins 0.000 description 329
- 206010028980 Neoplasm Diseases 0.000 description 210
- 238000011282 treatment Methods 0.000 description 69
- 210000000987 immune system Anatomy 0.000 description 65
- 210000004698 lymphocyte Anatomy 0.000 description 61
- 210000004443 dendritic cell Anatomy 0.000 description 58
- 102000004127 Cytokines Human genes 0.000 description 47
- 108090000695 Cytokines Proteins 0.000 description 47
- 210000001165 lymph node Anatomy 0.000 description 44
- 230000000694 effects Effects 0.000 description 42
- 230000008595 infiltration Effects 0.000 description 42
- 238000001764 infiltration Methods 0.000 description 42
- 239000000427 antigen Substances 0.000 description 41
- 108091007433 antigens Proteins 0.000 description 41
- 102000036639 antigens Human genes 0.000 description 41
- 201000011510 cancer Diseases 0.000 description 39
- 230000028993 immune response Effects 0.000 description 39
- 230000004083 survival effect Effects 0.000 description 37
- 230000007246 mechanism Effects 0.000 description 32
- 230000004044 response Effects 0.000 description 31
- 238000000684 flow cytometry Methods 0.000 description 29
- 210000003719 b-lymphocyte Anatomy 0.000 description 28
- 230000003053 immunization Effects 0.000 description 28
- 238000002649 immunization Methods 0.000 description 28
- 230000006378 damage Effects 0.000 description 26
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 25
- 230000004913 activation Effects 0.000 description 25
- 108010039471 Fas Ligand Protein Proteins 0.000 description 23
- 230000007423 decrease Effects 0.000 description 23
- 230000001404 mediated effect Effects 0.000 description 22
- 238000010186 staining Methods 0.000 description 22
- 230000001939 inductive effect Effects 0.000 description 20
- 210000005259 peripheral blood Anatomy 0.000 description 20
- 239000011886 peripheral blood Substances 0.000 description 20
- 102000003812 Interleukin-15 Human genes 0.000 description 19
- 108090000172 Interleukin-15 Proteins 0.000 description 19
- 238000010790 dilution Methods 0.000 description 19
- 239000012895 dilution Substances 0.000 description 19
- 238000002474 experimental method Methods 0.000 description 19
- 238000004519 manufacturing process Methods 0.000 description 19
- 108090000397 Caspase 3 Proteins 0.000 description 18
- 102100029855 Caspase-3 Human genes 0.000 description 18
- 206010063397 Rosai-Dorfman syndrome Diseases 0.000 description 18
- 208000006489 Sinus Histiocytosis Diseases 0.000 description 18
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 17
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 17
- 108010002586 Interleukin-7 Proteins 0.000 description 17
- 102000000704 Interleukin-7 Human genes 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000012636 effector Substances 0.000 description 17
- 230000006870 function Effects 0.000 description 16
- 108091008611 Protein Kinase B Proteins 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- 230000001506 immunosuppresive effect Effects 0.000 description 15
- 102000011727 Caspases Human genes 0.000 description 14
- 108010076667 Caspases Proteins 0.000 description 14
- 230000000903 blocking effect Effects 0.000 description 14
- 238000011533 pre-incubation Methods 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 13
- 230000000259 anti-tumor effect Effects 0.000 description 13
- 230000001413 cellular effect Effects 0.000 description 13
- 238000002512 chemotherapy Methods 0.000 description 13
- 238000011534 incubation Methods 0.000 description 13
- 210000003071 memory t lymphocyte Anatomy 0.000 description 13
- 230000037361 pathway Effects 0.000 description 13
- 238000002560 therapeutic procedure Methods 0.000 description 13
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 12
- 229960000074 biopharmaceutical Drugs 0.000 description 12
- 210000002540 macrophage Anatomy 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 230000001629 suppression Effects 0.000 description 12
- 230000030741 antigen processing and presentation Effects 0.000 description 11
- 210000002865 immune cell Anatomy 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000012528 membrane Substances 0.000 description 11
- 230000015654 memory Effects 0.000 description 11
- 238000001959 radiotherapy Methods 0.000 description 11
- 210000003289 regulatory T cell Anatomy 0.000 description 11
- 108090000672 Annexin A5 Proteins 0.000 description 10
- 102000004121 Annexin A5 Human genes 0.000 description 10
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 10
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 10
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 10
- 229930040373 Paraformaldehyde Natural products 0.000 description 10
- 239000002671 adjuvant Substances 0.000 description 10
- 239000013000 chemical inhibitor Substances 0.000 description 10
- 238000013467 fragmentation Methods 0.000 description 10
- 238000006062 fragmentation reaction Methods 0.000 description 10
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 10
- 230000002601 intratumoral effect Effects 0.000 description 10
- 210000000265 leukocyte Anatomy 0.000 description 10
- 229920002866 paraformaldehyde Polymers 0.000 description 10
- 230000002633 protecting effect Effects 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 9
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 9
- 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 9
- 206010062016 Immunosuppression Diseases 0.000 description 9
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 9
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 102000055102 bcl-2-Associated X Human genes 0.000 description 9
- 230000030833 cell death Effects 0.000 description 9
- 230000034994 death Effects 0.000 description 9
- 231100000517 death Toxicity 0.000 description 9
- 230000003828 downregulation Effects 0.000 description 9
- 201000010536 head and neck cancer Diseases 0.000 description 9
- 208000014829 head and neck neoplasm Diseases 0.000 description 9
- 230000001976 improved effect Effects 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 238000002203 pretreatment Methods 0.000 description 9
- 108090000567 Caspase 7 Proteins 0.000 description 8
- 102100038902 Caspase-7 Human genes 0.000 description 8
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 8
- 102100024481 Signal transducer and activator of transcription 5A Human genes 0.000 description 8
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 8
- 230000002424 anti-apoptotic effect Effects 0.000 description 8
- 230000001640 apoptogenic effect Effects 0.000 description 8
- 238000003501 co-culture Methods 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 230000007547 defect Effects 0.000 description 8
- 230000007123 defense Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 210000003162 effector t lymphocyte Anatomy 0.000 description 8
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 8
- 238000003364 immunohistochemistry Methods 0.000 description 8
- 230000009545 invasion Effects 0.000 description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 7
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 7
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 7
- 102100025752 CASP8 and FADD-like apoptosis regulator Human genes 0.000 description 7
- 206010016654 Fibrosis Diseases 0.000 description 7
- 101000914211 Homo sapiens CASP8 and FADD-like apoptosis regulator Proteins 0.000 description 7
- 239000004698 Polyethylene Substances 0.000 description 7
- 230000000890 antigenic effect Effects 0.000 description 7
- 230000004761 fibrosis Effects 0.000 description 7
- 230000008629 immune suppression Effects 0.000 description 7
- 230000036039 immunity Effects 0.000 description 7
- 230000035800 maturation Effects 0.000 description 7
- 210000005087 mononuclear cell Anatomy 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 230000004936 stimulating effect Effects 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 230000003827 upregulation Effects 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 101100322915 Caenorhabditis elegans akt-1 gene Proteins 0.000 description 6
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 6
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 6
- 102100025136 Macrosialin Human genes 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- -1 chemical inhibitors Chemical class 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229960004397 cyclophosphamide Drugs 0.000 description 6
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 6
- 230000004064 dysfunction Effects 0.000 description 6
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 6
- 210000002443 helper t lymphocyte Anatomy 0.000 description 6
- 238000011532 immunohistochemical staining Methods 0.000 description 6
- 239000003550 marker Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 210000001700 mitochondrial membrane Anatomy 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 6
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 5
- 229940126638 Akt inhibitor Drugs 0.000 description 5
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 5
- 206010028851 Necrosis Diseases 0.000 description 5
- 108091007960 PI3Ks Proteins 0.000 description 5
- 239000002033 PVDF binder Substances 0.000 description 5
- MIFGOLAMNLSLGH-QOKNQOGYSA-N Z-Val-Ala-Asp(OMe)-CH2F Chemical compound COC(=O)C[C@@H](C(=O)CF)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1 MIFGOLAMNLSLGH-QOKNQOGYSA-N 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- 230000005975 antitumor immune response Effects 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 229940022399 cancer vaccine Drugs 0.000 description 5
- 238000009566 cancer vaccine Methods 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000002708 enhancing effect Effects 0.000 description 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 238000009169 immunotherapy Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 229960000905 indomethacin Drugs 0.000 description 5
- 239000000411 inducer Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000017074 necrotic cell death Effects 0.000 description 5
- 229940127255 pan-caspase inhibitor Drugs 0.000 description 5
- 230000003836 peripheral circulation Effects 0.000 description 5
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 5
- 230000000861 pro-apoptotic effect Effects 0.000 description 5
- 239000003197 protein kinase B inhibitor Substances 0.000 description 5
- 230000005855 radiation Effects 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 230000036962 time dependent Effects 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 4
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 4
- 101150013553 CD40 gene Proteins 0.000 description 4
- 102100035793 CD83 antigen Human genes 0.000 description 4
- UGTJLJZQQFGTJD-UHFFFAOYSA-N Carbonylcyanide-3-chlorophenylhydrazone Chemical compound ClC1=CC=CC(NN=C(C#N)C#N)=C1 UGTJLJZQQFGTJD-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 4
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 4
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 4
- 102000003945 NF-kappa B Human genes 0.000 description 4
- 108010057466 NF-kappa B Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000006044 T cell activation Effects 0.000 description 4
- 230000033540 T cell apoptotic process Effects 0.000 description 4
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 4
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000003915 cell function Effects 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000004041 dendritic cell maturation Effects 0.000 description 4
- 230000030609 dephosphorylation Effects 0.000 description 4
- 238000006209 dephosphorylation reaction Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 4
- 229930182490 saponin Natural products 0.000 description 4
- 150000007949 saponins Chemical class 0.000 description 4
- 230000001960 triggered effect Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- ZCXUVYAZINUVJD-AHXZWLDOSA-N 2-deoxy-2-((18)F)fluoro-alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H]([18F])[C@@H](O)[C@@H]1O ZCXUVYAZINUVJD-AHXZWLDOSA-N 0.000 description 3
- IWCQHVUQEFDRIW-UHFFFAOYSA-N 3-[1-[[4-(6-phenyl-8H-imidazo[4,5-g]quinoxalin-7-yl)phenyl]methyl]piperidin-4-yl]-1H-benzimidazol-2-one Chemical compound O=c1[nH]c2ccccc2n1C1CCN(Cc2ccc(cc2)-c2[nH]c3cc4ncnc4cc3nc2-c2ccccc2)CC1 IWCQHVUQEFDRIW-UHFFFAOYSA-N 0.000 description 3
- 102000004039 Caspase-9 Human genes 0.000 description 3
- 108090000566 Caspase-9 Proteins 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 241000252210 Cyprinidae Species 0.000 description 3
- 230000005778 DNA damage Effects 0.000 description 3
- 231100000277 DNA damage Toxicity 0.000 description 3
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 3
- 101000911513 Homo sapiens Uncharacterized protein FAM215A Proteins 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 3
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 3
- 102100026728 Uncharacterized protein FAM215A Human genes 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 238000003782 apoptosis assay Methods 0.000 description 3
- 230000005775 apoptotic pathway Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000002591 computed tomography Methods 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000003394 haemopoietic effect Effects 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 230000006058 immune tolerance Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 210000002751 lymph Anatomy 0.000 description 3
- 230000001926 lymphatic effect Effects 0.000 description 3
- 239000011325 microbead Substances 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 210000004986 primary T-cell Anatomy 0.000 description 3
- 230000005522 programmed cell death Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 150000003180 prostaglandins Chemical class 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000004654 survival pathway Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000012130 whole-cell lysate Substances 0.000 description 3
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 102000000412 Annexin Human genes 0.000 description 2
- 108050008874 Annexin Proteins 0.000 description 2
- 229940088872 Apoptosis inhibitor Drugs 0.000 description 2
- 102000051485 Bcl-2 family Human genes 0.000 description 2
- 108700038897 Bcl-2 family Proteins 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 229940123169 Caspase inhibitor Drugs 0.000 description 2
- 102100026548 Caspase-8 Human genes 0.000 description 2
- 108090000538 Caspase-8 Proteins 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 108010060123 Conjugate Vaccines Proteins 0.000 description 2
- 231100001074 DNA strand break Toxicity 0.000 description 2
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 102000006354 HLA-DR Antigens Human genes 0.000 description 2
- 108010058597 HLA-DR Antigens Proteins 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 101150021539 MT-CO2 gene Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108091093105 Nuclear DNA Proteins 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- 102100024784 Suppressor of cytokine signaling 2 Human genes 0.000 description 2
- 101710137422 Suppressor of cytokine signaling 2 Proteins 0.000 description 2
- 230000006052 T cell proliferation Effects 0.000 description 2
- 238000012288 TUNEL assay Methods 0.000 description 2
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 2
- 108091005956 Type II transmembrane proteins Proteins 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000006786 activation induced cell death Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940037003 alum Drugs 0.000 description 2
- JKOQGQFVAUAYPM-UHFFFAOYSA-N amifostine Chemical compound NCCCNCCSP(O)(O)=O JKOQGQFVAUAYPM-UHFFFAOYSA-N 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000000158 apoptosis inhibitor Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 239000003124 biologic agent Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000007969 cellular immunity Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 239000000562 conjugate Substances 0.000 description 2
- 229940031670 conjugate vaccine Drugs 0.000 description 2
- 230000003138 coordinated effect Effects 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000009462 endogenous apoptosis Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036732 histological change Effects 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000010212 intracellular staining Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000027829 mitochondrial depolarization Effects 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 230000006667 mitochondrial pathway Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 210000004049 perilymph Anatomy 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 230000005909 tumor killing Effects 0.000 description 2
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- YIWGJFPJRAEKMK-UHFFFAOYSA-N 1-(2H-benzotriazol-5-yl)-3-methyl-8-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione Chemical compound CN1C(=O)N(c2ccc3n[nH]nc3c2)C2(CCN(CC2)C(=O)c2cnc(NCc3cccc(OC(F)(F)F)c3)nc2)C1=O YIWGJFPJRAEKMK-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 238000010176 18-FDG-positron emission tomography Methods 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- PWVRXSQPCQPQHM-UHFFFAOYSA-N 2-(4-aminophenyl)-1h-indol-6-amine Chemical compound C1=CC(N)=CC=C1C1=CC2=CC=C(N)C=C2N1 PWVRXSQPCQPQHM-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- YPSXFMHXRZAGTG-UHFFFAOYSA-N 4-methoxy-2-[2-(5-methoxy-2-nitrosophenyl)ethyl]-1-nitrosobenzene Chemical compound COC1=CC=C(N=O)C(CCC=2C(=CC=C(OC)C=2)N=O)=C1 YPSXFMHXRZAGTG-UHFFFAOYSA-N 0.000 description 1
- 101150107888 AKT2 gene Proteins 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- 102000007272 Apoptosis Inducing Factor Human genes 0.000 description 1
- 108010033604 Apoptosis Inducing Factor Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 108091007065 BIRCs Proteins 0.000 description 1
- 210000005236 CD8+ effector T cell Anatomy 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 101800004419 Cleaved form Proteins 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- 102000009058 Death Domain Receptors Human genes 0.000 description 1
- 108010049207 Death Domain Receptors Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000007989 Effector Caspases Human genes 0.000 description 1
- 108010089510 Effector Caspases Proteins 0.000 description 1
- 206010053430 Erythrophagocytosis Diseases 0.000 description 1
- 229940032072 GVAX vaccine Drugs 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101000638161 Homo sapiens Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 101150069380 JAK3 gene Proteins 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 101150079116 MT-CO1 gene Proteins 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 1
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108010073443 Ribi adjuvant Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010040742 Sinus congestion Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 230000017274 T cell anergy Effects 0.000 description 1
- 108091008035 T cell costimulatory receptors Proteins 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 101710112792 Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 101150045355 akt1 gene Proteins 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 229960001097 amifostine Drugs 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 108010091987 aposome Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 239000000298 carbocyanine Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000012578 cell culture reagent Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002038 chemiluminescence detection Methods 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 108091008034 costimulatory receptors Proteins 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 238000009295 crossflow filtration Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 230000000445 cytocidal effect Effects 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940124569 cytoprotecting agent Drugs 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 238000001739 density measurement Methods 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000011496 digital image analysis Methods 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 230000008519 endogenous mechanism Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229940098617 ethyol Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000034725 extrinsic apoptotic signaling pathway Effects 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000007849 functional defect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 210000002861 immature t-cell Anatomy 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000008004 immune attack Effects 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 238000011502 immune monitoring Methods 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 230000000899 immune system response Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 238000013394 immunophenotyping Methods 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000005468 ion implantation Methods 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000005427 lymphocyte apoptotic process Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 210000004479 myeloid suppressor cell Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000006036 negative regulation of mitochondrial membrane potential Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000101 novel biomarker Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000863 peptide conjugate Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- QWYZFXLSWMXLDM-UHFFFAOYSA-M pinacyanol iodide Chemical compound [I-].C1=CC2=CC=CC=C2N(CC)C1=CC=CC1=CC=C(C=CC=C2)C2=[N+]1CC QWYZFXLSWMXLDM-UHFFFAOYSA-M 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000001686 pro-survival effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- YSQDQEOIFWWVHA-UHFFFAOYSA-A promune Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].CC1=C(C(=O)NC(N)=C)N=CN1C1OC(COP([O-])(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP([O-])(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP([O-])(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP([O-])(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)CO)C(OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP([O-])(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP([O-])(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP([O-])(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP([O-])(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)O)C1 YSQDQEOIFWWVHA-UHFFFAOYSA-A 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229940034080 provenge Drugs 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000007755 survival signaling Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 108010069784 vitespin Proteins 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 108010065816 zeta chain antigen T cell receptor Proteins 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Nutrition Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99075907P | 2007-11-28 | 2007-11-28 | |
| US60/990,759 | 2007-11-28 | ||
| US5692508P | 2008-05-29 | 2008-05-29 | |
| US61/056,925 | 2008-05-29 | ||
| PCT/US2008/084789 WO2009070639A1 (en) | 2007-11-28 | 2008-11-26 | Method of increasing immunological effect |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011504932A JP2011504932A (ja) | 2011-02-17 |
| JP2011504932A5 JP2011504932A5 (enExample) | 2013-05-23 |
| JP5563472B2 true JP5563472B2 (ja) | 2014-07-30 |
Family
ID=40678966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010536148A Expired - Fee Related JP5563472B2 (ja) | 2007-11-28 | 2008-11-26 | 免疫学的効果を増大させる方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US7993660B2 (enExample) |
| EP (1) | EP2234642B8 (enExample) |
| JP (1) | JP5563472B2 (enExample) |
| AU (1) | AU2008329741B2 (enExample) |
| CA (1) | CA2706445C (enExample) |
| DK (1) | DK2234642T3 (enExample) |
| ES (1) | ES2653887T3 (enExample) |
| MX (1) | MX2010005718A (enExample) |
| WO (1) | WO2009070639A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070154399A1 (en) * | 2000-10-27 | 2007-07-05 | Hadden John W | Immunotherapy for immune suppressed patients |
| US20070031372A1 (en) * | 2004-08-05 | 2007-02-08 | Hadden John W | Vaccine immunotherapy for immune suppressed patients |
| CA2950109C (en) | 2000-10-27 | 2019-02-19 | John W. Hadden | Vaccine immunotherapy for immune suppressed patients |
| US20070025958A1 (en) * | 2000-10-27 | 2007-02-01 | Hadden John W | Vaccine immunotherapy |
| ES2736726T3 (es) * | 2006-03-09 | 2020-01-07 | Aethlon Medical Inc | Eliminación extracorpórea de partículas microvesiculares |
| AU2008329741B2 (en) | 2007-11-28 | 2013-09-12 | Irx Therapeutics, Inc. | Method of increasing immunological effect |
| AU2009251277A1 (en) * | 2008-05-29 | 2009-12-03 | Irx Therapeutics, Inc. | Mechanism of action of primary cell derived biologic |
| CA3017298C (en) | 2009-05-15 | 2021-09-28 | Irx Therapeutics, Inc. | Compositions comprising primary cell-derived biologics for enhancing immune responses in patients |
| CN103097543A (zh) | 2009-12-08 | 2013-05-08 | 伊尔克斯治疗有限公司 | 逆转朗格汉斯细胞免疫抑制的方法 |
| MX2016001304A (es) | 2013-07-30 | 2016-04-07 | Gilead Connecticut Inc | Polimorfo de inhibidores de syk. |
| TWI735853B (zh) | 2013-12-23 | 2021-08-11 | 美商克洛諾斯生技有限公司 | 脾酪胺酸激酶抑制劑 |
| CN115028640A (zh) | 2017-08-25 | 2022-09-09 | 吉利德科学公司 | Syk抑制剂的多晶型物 |
| KR20210131372A (ko) | 2019-02-22 | 2021-11-02 | 크로노스 바이오, 인코포레이티드 | Syk 억제제로서의 축합된 피라진의 고체 형태 |
| FI20237105A1 (en) | 2023-05-29 | 2024-11-30 | Onni Biotechnologies Oy | Modified natural killer cells with enhanced cytotoxic action and greater survival |
Family Cites Families (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4079127A (en) | 1976-10-28 | 1978-03-14 | Board Of Regents Of The University Of Texas | Thymosin alpha 1 |
| US4116951A (en) | 1977-04-22 | 1978-09-26 | Hoffmann-La Roche Inc. | [Asn2 ]-thymosin α1 and analogs thereof |
| US4148788A (en) | 1978-01-23 | 1979-04-10 | Hoffmann-La Roche Inc. | Synthesis of thymosin α1 |
| DE2919592A1 (de) | 1979-05-15 | 1981-01-15 | Max Planck Gesellschaft | Verfahren zur herstellung von thymosin- alpha 1 und derivaten davon |
| DE3100974A1 (de) | 1980-01-18 | 1982-01-21 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | Thymosin(alpha)(pfeil abwaerts)1(pfeil abwaerts)-fragmente enthaltende arzneimittel mit immunregulierender wirkung, und thymosin(alpha)(pfeil abwaerts)1(pfeil abwaerts)-fragmente |
| US4470926A (en) | 1980-01-18 | 1984-09-11 | Max-Planck-Gesellschaft zur F/o/ rderung der Wissenschaften e.V. | Medicaments containing thymosin alpha 1 fragments and having an immunostimulant action, and fragments of thymosin alpha 1 |
| US4612365A (en) | 1980-03-25 | 1986-09-16 | Max-Planck-Gesellschaft Zur Foederung Der Wissenschaften | Medicaments containing alpha 1-thymosin and having an immuno regulatory action and alpha 1-thymosin fragments |
| US4293455A (en) | 1980-04-07 | 1981-10-06 | Rockefeller University | N.sup.α -Desacetylthymosinα1 and process |
| IL62903A0 (en) | 1980-05-22 | 1981-07-31 | Deutsches Krebsforsch | Method for the production of interferon ii and stimulated clones for the carrying out of the method |
| US4390623A (en) | 1980-10-02 | 1983-06-28 | Hooper Trading Company | Serum-free and mitogen-free T-cell growth factor and process for making same |
| US4464355A (en) | 1981-03-26 | 1984-08-07 | Hooper Trading Co. | Serum-free and mitogen-free T-cell growth factor and process for making same |
| US4448879A (en) | 1981-03-26 | 1984-05-15 | Hooper Trading Company | High yield process for in vitro production of serum-free and mitogen-free interleukin-2 |
| US4406830A (en) | 1981-04-17 | 1983-09-27 | Shanksville Corporation, N.V. | Regulatory glycoprotein for immune response and the use thereof in the production of T-cell growth factor |
| US4504415A (en) | 1983-04-04 | 1985-03-12 | Hoffman-La Roche Inc. | Synthesis of thymosin α1 and desacetyl thymosin α1 |
| US4614731A (en) | 1983-09-15 | 1986-09-30 | Hoffmann-La Roche Inc. | Peptide having immunopotentiating activity similar to thymosin alpha1 |
| US4659694A (en) | 1983-10-27 | 1987-04-21 | Hoffmann-La Roche Inc. | Prothymosin alpha |
| US4716148A (en) | 1984-08-13 | 1987-12-29 | Hoffman-La Roche Inc. | Prothymosin alpha |
| US5503841A (en) | 1985-09-20 | 1996-04-02 | Cetus Oncology Corporation | Human IL-2 as a vaccine adjuvant |
| US5643565A (en) | 1985-09-20 | 1997-07-01 | Chiron Corporation | Human IL-2 as a vaccine adjuvant |
| US5100664A (en) | 1985-09-20 | 1992-03-31 | Cetus Corporation | Human IL-2 as a vaccine adjuvant |
| US5098702A (en) | 1986-04-09 | 1992-03-24 | Cetus Corporation | Combination therapy using interleukin-2 and tumor necrosis factor |
| JPS63503308A (ja) | 1986-05-09 | 1988-12-02 | スローン‐ケツテリング・インステイテユート・フオー・キヤンサー・リサーチ | 抗腫瘍療法のためのリポ多糖体及び天然因子の組成物及び治療方法 |
| SE8801426D0 (sv) | 1988-04-15 | 1988-04-15 | Ulf Rothman | Forfarande och medel for blodbehandling |
| IL92382A (en) | 1988-11-23 | 1994-12-29 | Univ Michigan | Use of a ligand specific for CD28 in the manufacture of medicament |
| US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
| IT1238231B (it) | 1989-12-18 | 1993-07-12 | Consiglio Nazionale Ricerche | Impiego di immunomodulanti come agenti sinergici di chemioterapici nella terapia dei tumori |
| KR100223255B1 (ko) | 1992-02-10 | 1999-10-15 | 더글라스 테스타 | 개량된 알파 인터페론 조성물 및 인간 말초혈 백혈구로 부터의 제조 방법 |
| CA2139756A1 (en) | 1992-07-08 | 1994-01-20 | Eric M. Bonnem | Use of gm-csf as a vaccine adjuvant |
| US5828784A (en) * | 1992-07-13 | 1998-10-27 | Hitachi Denshi Kabushiki Kaisha | Data coding method and apparatus using a plurality of blocks of different length |
| US6161122A (en) * | 1992-12-10 | 2000-12-12 | Hawkes; Calvert T. | Method and apparatus for interactively providing information at multiple sites |
| CN1094310A (zh) | 1992-12-15 | 1994-11-02 | 托马斯·C·梅里根 | 人体免疫缺陷性病毒感染用组合式化学疗法 |
| US5747024A (en) | 1993-03-08 | 1998-05-05 | Immunex Corporation | Vaccine adjuvant comprising interleukin-15 |
| DK0700430T3 (da) * | 1993-06-04 | 2005-08-15 | Us Navy | Fremgangsmåder til selektivt af stimulere proliferation af T-celler |
| CN1044781C (zh) | 1994-02-05 | 1999-08-25 | 丹东市生物制品免疫技术应用研究中心 | 复方免疫抗生素 |
| DE4412794A1 (de) | 1994-04-14 | 1995-12-14 | Univ Ludwigs Albert | Verfahren zur Herstellung von dendritischen Zellen, so erhaltene Zellen und Behälter zur Durchführung dieses Verfahrens |
| EP0789588B1 (en) | 1994-11-17 | 2005-01-19 | University Of South Florida | Method for making a medicament for treating secondary immunodeficiency |
| US5632983A (en) | 1994-11-17 | 1997-05-27 | University Of South Florida | Method for treating secondary immunodeficiency |
| DE69628921T2 (de) | 1995-05-04 | 2004-04-22 | The Government Of The United States Of America As Represented By The Secretary Of The Navy | Verfahren zur modulation der t-zell-überlebensrate durch von bcl-xl protein-spiegels |
| US5788963A (en) | 1995-07-31 | 1998-08-04 | Pacific Northwest Cancer Foundation | Isolation and/or preservation of dendritic cells for prostate cancer immunotherapy |
| NZ331369A (en) | 1996-02-21 | 2001-04-27 | Franco Lori | Use of a genetic construct that directs virus expression in a lymphoid organ or a transduced cell thereof for genetic immunization |
| US5849589A (en) | 1996-03-11 | 1998-12-15 | Duke University | Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells |
| US6017527A (en) | 1996-07-10 | 2000-01-25 | Immunex Corporation | Activated dendritic cells and methods for their activation |
| US5849307A (en) | 1997-03-26 | 1998-12-15 | The Picower Institute For Medical Research | Vaccine adjuvant |
| AU748467B2 (en) | 1997-10-17 | 2002-06-06 | University Of South Florida | Method to diagnose and monitor cellular immune deficiencies |
| ATE428769T1 (de) | 1997-10-27 | 2009-05-15 | Univ Rockefeller | Methode und zusammensetzung zur herstellung von reifen dendritischen zellen |
| US20050124645A1 (en) * | 1998-04-20 | 2005-06-09 | Finkel Terri H. | Methods and compositions for increasing CD4lymphocyte immune responsiveness |
| EP0974357A1 (en) | 1998-07-16 | 2000-01-26 | Schering-Plough | Chemokines as adjuvants of immune response |
| US6350589B1 (en) | 1998-12-31 | 2002-02-26 | Viragen, Inc. | Compositions of highly-purified natural mixtures of type I interferon derived from leukocytes and methods |
| US7056503B2 (en) | 1999-08-19 | 2006-06-06 | Regents Of The University Of Michigan | Enclosures housing cell-coated supports for treating tumors |
| US6406699B1 (en) | 1999-10-05 | 2002-06-18 | Gary W. Wood | Composition and method of cancer antigen immunotherapy |
| DK1257632T3 (da) | 2000-02-24 | 2008-01-28 | Xcyte Therapies Inc | Samtidig stimulering og opkoncentrering af celler |
| US7266501B2 (en) * | 2000-03-02 | 2007-09-04 | Akiba Electronics Institute Llc | Method and apparatus for accommodating primary content audio and secondary content remaining audio capability in the digital audio production process |
| US7182942B2 (en) | 2000-10-27 | 2007-02-27 | Irx Therapeutics, Inc. | Vaccine immunotherapy for immune suppressed patients |
| US20070025958A1 (en) | 2000-10-27 | 2007-02-01 | Hadden John W | Vaccine immunotherapy |
| US20060194242A1 (en) | 2000-10-27 | 2006-08-31 | Hadden John W | Immunotherapy for immune suppressed patients |
| CA2950109C (en) * | 2000-10-27 | 2019-02-19 | John W. Hadden | Vaccine immunotherapy for immune suppressed patients |
| US20070031372A1 (en) | 2004-08-05 | 2007-02-08 | Hadden John W | Vaccine immunotherapy for immune suppressed patients |
| US20070154399A1 (en) | 2000-10-27 | 2007-07-05 | Hadden John W | Immunotherapy for immune suppressed patients |
| JP2005510491A (ja) | 2001-10-26 | 2005-04-21 | イミュノ−アールエックス, インコーポレイテッド | 免疫抑制を逆転させるための免疫治療 |
| DE10154579A1 (de) | 2001-11-07 | 2003-05-28 | Medigene Ag | Topikale Verwendung von Cytokinen und Chemokinen zur Behandlung von viralen oder mykotischen Hauterkrankungen oder Tumorerkrankungen |
| WO2003061566A2 (en) | 2002-01-24 | 2003-07-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Anti-cancer combination and use thereof |
| CA2511815A1 (en) | 2002-12-26 | 2004-07-22 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates of cytokines, chemokines, growth factors, polypeptide hormones and antagonists thereof with preserved receptor-binding activity |
| US6896879B2 (en) | 2003-07-03 | 2005-05-24 | Cel-Sci Corporation | Method of pre-sensitizing cancer prior to treatment with radiation and/or chemotherapy and a novel cytokine mixture |
| WO2005077048A2 (en) * | 2004-02-09 | 2005-08-25 | The Johns Hopkins University | Immune modulation by regulating expression of the “minor” gene in immune dendritic cells |
| GB0409799D0 (en) | 2004-04-30 | 2004-06-09 | Isis Innovation | Method of generating improved immune response |
| ES2553133T3 (es) | 2004-06-04 | 2015-12-04 | Cel-Sci Corporation | Método de modificación de la proporción de CD4/CD8 y del infiltrado celular mononuclear en un tumor |
| KR100773539B1 (ko) * | 2004-07-14 | 2007-11-05 | 삼성전자주식회사 | 멀티채널 오디오 데이터 부호화/복호화 방법 및 장치 |
| US20070065415A1 (en) * | 2005-09-16 | 2007-03-22 | Kleinsek Donald A | Compositions and methods for the augmentation and repair of defects in tissue |
| US20090181078A1 (en) | 2006-09-26 | 2009-07-16 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
| CA2691539C (en) | 2007-06-21 | 2014-08-26 | Angelica Therapeutics, Inc. | Modified toxins |
| AU2008329741B2 (en) | 2007-11-28 | 2013-09-12 | Irx Therapeutics, Inc. | Method of increasing immunological effect |
| WO2009137238A2 (en) | 2008-04-14 | 2009-11-12 | Irx Therapeutics, Inc. | Irx-2 modified manufacturing process |
| AU2009251277A1 (en) | 2008-05-29 | 2009-12-03 | Irx Therapeutics, Inc. | Mechanism of action of primary cell derived biologic |
| CA3017298C (en) | 2009-05-15 | 2021-09-28 | Irx Therapeutics, Inc. | Compositions comprising primary cell-derived biologics for enhancing immune responses in patients |
| CN103097543A (zh) | 2009-12-08 | 2013-05-08 | 伊尔克斯治疗有限公司 | 逆转朗格汉斯细胞免疫抑制的方法 |
-
2008
- 2008-11-26 AU AU2008329741A patent/AU2008329741B2/en not_active Ceased
- 2008-11-26 EP EP08854580.1A patent/EP2234642B8/en active Active
- 2008-11-26 JP JP2010536148A patent/JP5563472B2/ja not_active Expired - Fee Related
- 2008-11-26 DK DK08854580.1T patent/DK2234642T3/en active
- 2008-11-26 WO PCT/US2008/084789 patent/WO2009070639A1/en not_active Ceased
- 2008-11-26 CA CA2706445A patent/CA2706445C/en active Active
- 2008-11-26 MX MX2010005718A patent/MX2010005718A/es not_active Application Discontinuation
- 2008-11-26 US US12/323,595 patent/US7993660B2/en active Active
- 2008-11-26 ES ES08854580.1T patent/ES2653887T3/es active Active
-
2011
- 2011-08-08 US US13/205,229 patent/US8591956B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CA2706445A1 (en) | 2009-06-04 |
| US20090155291A1 (en) | 2009-06-18 |
| WO2009070639A1 (en) | 2009-06-04 |
| EP2234642B1 (en) | 2017-09-27 |
| US8591956B2 (en) | 2013-11-26 |
| AU2008329741A1 (en) | 2009-06-04 |
| US20120141512A1 (en) | 2012-06-07 |
| AU2008329741B2 (en) | 2013-09-12 |
| EP2234642B8 (en) | 2017-11-01 |
| US7993660B2 (en) | 2011-08-09 |
| CA2706445C (en) | 2019-07-23 |
| EP2234642A1 (en) | 2010-10-06 |
| JP2011504932A (ja) | 2011-02-17 |
| MX2010005718A (es) | 2010-08-10 |
| ES2653887T3 (es) | 2018-02-09 |
| EP2234642A4 (en) | 2012-04-25 |
| DK2234642T3 (en) | 2018-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5563472B2 (ja) | 免疫学的効果を増大させる方法 | |
| US20240279352A1 (en) | Methods and compositions for modifying macrophage polarization into pro-inflammatory cells to treat cancer | |
| TW202015732A (zh) | 免疫檢查點阻礙藥的有效性判定用生物標記 | |
| EP3638293B1 (en) | Compositions for treating cancer | |
| US20200399377A1 (en) | Combination cancer therapy with anti-cancer agents and antibodies targeting a complex comprising non-classical hla-i and neoantigen | |
| US20220040230A1 (en) | Compositions and methods for immunotherapies | |
| Kosianova et al. | Regulation of cancer stem cells and immunotherapy of glioblastoma | |
| US20110081313A1 (en) | Mechanism of action of primary cell derived biologic | |
| US20220354811A1 (en) | Methods and compositions for modulating macrophages polarization | |
| CN118317778A (zh) | 工程化nk细胞及其用途 | |
| HK1150303A (en) | Method of increasing immunological effect | |
| HK1150303B (en) | Method of increasing immunological effect | |
| JP2021523359A (ja) | 併用療法のための患者の選択 | |
| CA3071217A1 (en) | Hsp70 based combination therapy | |
| US20210100859A1 (en) | Herpes simplex virus (hsv) anticancer therapies | |
| JP2025179057A (ja) | 併用療法のための患者の選択 | |
| JP2023543163A (ja) | 造血細胞移植後の血液新生物再発の処置または予防で使用するためのmdm2阻害剤 | |
| TW202037392A (zh) | 包含基於樹突細胞之疫苗與免疫檢查點抑制劑之組合治療 | |
| Fletcher | The Role of NSAID-Induced ER Stress and Immunomodulation in the Suppression of Colorectal Tumorigenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111020 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130402 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130624 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130921 |
|
| 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: 20140519 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140612 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5563472 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |