CA3066048A1 - Combination therapy - Google Patents
Combination therapy Download PDFInfo
- Publication number
- CA3066048A1 CA3066048A1 CA3066048A CA3066048A CA3066048A1 CA 3066048 A1 CA3066048 A1 CA 3066048A1 CA 3066048 A CA3066048 A CA 3066048A CA 3066048 A CA3066048 A CA 3066048A CA 3066048 A1 CA3066048 A1 CA 3066048A1
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- icos
- antigen binding
- binding portion
- human
- 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.)
- Pending
Links
- 238000002648 combination therapy Methods 0.000 title description 3
- 230000027455 binding Effects 0.000 claims abstract description 252
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 247
- 239000000427 antigen Substances 0.000 claims abstract description 196
- 108091007433 antigens Proteins 0.000 claims abstract description 196
- 102000036639 antigens Human genes 0.000 claims abstract description 196
- 241000282414 Homo sapiens Species 0.000 claims abstract description 151
- 201000011510 cancer Diseases 0.000 claims abstract description 88
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 79
- 238000000034 method Methods 0.000 claims abstract description 65
- 239000012634 fragment Substances 0.000 claims abstract description 46
- 101001042104 Homo sapiens Inducible T-cell costimulator Proteins 0.000 claims abstract description 38
- 102000043396 human ICOS Human genes 0.000 claims abstract description 34
- 238000011282 treatment Methods 0.000 claims description 80
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims description 48
- 239000000556 agonist Substances 0.000 claims description 48
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 47
- 239000003814 drug Substances 0.000 claims description 32
- 102000048362 human PDCD1 Human genes 0.000 claims description 27
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 27
- 229960002621 pembrolizumab Drugs 0.000 claims description 25
- 108091033319 polynucleotide Proteins 0.000 claims description 20
- 102000040430 polynucleotide Human genes 0.000 claims description 20
- 239000002157 polynucleotide Substances 0.000 claims description 20
- 206010009944 Colon cancer Diseases 0.000 claims description 17
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 14
- 229940124060 PD-1 antagonist Drugs 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 229960003301 nivolumab Drugs 0.000 claims description 13
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims description 11
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 11
- 201000001441 melanoma Diseases 0.000 claims description 10
- 239000013598 vector Substances 0.000 claims description 9
- 238000012258 culturing Methods 0.000 claims description 7
- 238000001802 infusion Methods 0.000 claims description 7
- 206010027406 Mesothelioma Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 210000000481 breast Anatomy 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
- 230000002496 gastric effect Effects 0.000 claims description 4
- 230000002611 ovarian Effects 0.000 claims description 4
- 206010061818 Disease progression Diseases 0.000 claims description 2
- 230000005750 disease progression Effects 0.000 claims description 2
- 231100000402 unacceptable toxicity Toxicity 0.000 claims description 2
- 102000048776 human CD274 Human genes 0.000 claims 4
- 102100040678 Programmed cell death protein 1 Human genes 0.000 abstract description 22
- 101710089372 Programmed cell death protein 1 Proteins 0.000 abstract 1
- 102000053646 Inducible T-Cell Co-Stimulator Human genes 0.000 description 190
- 108700013161 Inducible T-Cell Co-Stimulator Proteins 0.000 description 190
- 210000004027 cell Anatomy 0.000 description 127
- 210000001744 T-lymphocyte Anatomy 0.000 description 108
- 241000699670 Mus sp. Species 0.000 description 74
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 69
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 69
- 230000014509 gene expression Effects 0.000 description 69
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 61
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 61
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 56
- 150000001875 compounds Chemical class 0.000 description 56
- SFHYNDMGZXWXBU-LIMNOBDPSA-N 6-amino-2-[[(e)-(3-formylphenyl)methylideneamino]carbamoylamino]-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1NC(=O)N\N=C\C1=CC=CC(C=O)=C1 SFHYNDMGZXWXBU-LIMNOBDPSA-N 0.000 description 41
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 38
- 241000699666 Mus <mouse, genus> Species 0.000 description 36
- 230000000694 effects Effects 0.000 description 36
- 108090000623 proteins and genes Proteins 0.000 description 36
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 32
- 210000004369 blood Anatomy 0.000 description 31
- 239000008280 blood Substances 0.000 description 31
- 102100034980 ICOS ligand Human genes 0.000 description 30
- 101710093458 ICOS ligand Proteins 0.000 description 29
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 28
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 28
- 102000014914 Carrier Proteins Human genes 0.000 description 28
- 108091008324 binding proteins Proteins 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 28
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 25
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 25
- 229940079593 drug Drugs 0.000 description 25
- 235000018102 proteins Nutrition 0.000 description 24
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 23
- 241001529936 Murinae Species 0.000 description 22
- 102000005962 receptors Human genes 0.000 description 22
- 108020003175 receptors Proteins 0.000 description 22
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 21
- 102000025171 antigen binding proteins Human genes 0.000 description 19
- 108091000831 antigen binding proteins Proteins 0.000 description 19
- 238000003556 assay Methods 0.000 description 19
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 18
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 18
- 208000032839 leukemia Diseases 0.000 description 18
- 230000004044 response Effects 0.000 description 18
- 238000000684 flow cytometry Methods 0.000 description 17
- 230000004083 survival effect Effects 0.000 description 17
- 102000004127 Cytokines Human genes 0.000 description 16
- 108090000695 Cytokines Proteins 0.000 description 16
- 238000011161 development Methods 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 16
- 230000001419 dependent effect Effects 0.000 description 15
- 239000012636 effector Substances 0.000 description 15
- 230000006870 function Effects 0.000 description 15
- 108060003951 Immunoglobulin Proteins 0.000 description 14
- 230000006044 T cell activation Effects 0.000 description 14
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 14
- 102000018358 immunoglobulin Human genes 0.000 description 14
- 230000006698 induction Effects 0.000 description 14
- 229940045513 CTLA4 antagonist Drugs 0.000 description 13
- 230000004913 activation Effects 0.000 description 13
- 230000000638 stimulation Effects 0.000 description 13
- 206010025323 Lymphomas Diseases 0.000 description 12
- 230000000259 anti-tumor effect Effects 0.000 description 12
- 210000001616 monocyte Anatomy 0.000 description 12
- 210000004881 tumor cell Anatomy 0.000 description 12
- 108010074708 B7-H1 Antigen Proteins 0.000 description 11
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 11
- 238000004132 cross linking Methods 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 239000013604 expression vector Substances 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 10
- 208000017604 Hodgkin disease Diseases 0.000 description 10
- 206010035226 Plasma cell myeloma Diseases 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 230000016396 cytokine production Effects 0.000 description 10
- 210000004443 dendritic cell Anatomy 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 238000001543 one-way ANOVA Methods 0.000 description 10
- 208000026310 Breast neoplasm Diseases 0.000 description 9
- 230000006052 T cell proliferation Effects 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 210000003719 b-lymphocyte Anatomy 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- 238000011002 quantification Methods 0.000 description 9
- 210000000952 spleen Anatomy 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 8
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 8
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 8
- 230000003213 activating effect Effects 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 8
- 210000003289 regulatory T cell Anatomy 0.000 description 8
- 238000009097 single-agent therapy Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- 206010006187 Breast cancer Diseases 0.000 description 7
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 7
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 7
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 7
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 7
- -1 IFN-y Proteins 0.000 description 7
- 108010002350 Interleukin-2 Proteins 0.000 description 7
- 102000000588 Interleukin-2 Human genes 0.000 description 7
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 7
- 208000034578 Multiple myelomas Diseases 0.000 description 7
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 7
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 7
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 7
- 230000008484 agonism Effects 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 230000001900 immune effect Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 201000000050 myeloid neoplasm Diseases 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 230000003442 weekly effect Effects 0.000 description 7
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 6
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 102100021317 Inducible T-cell costimulator Human genes 0.000 description 6
- 102000003814 Interleukin-10 Human genes 0.000 description 6
- 108090000174 Interleukin-10 Proteins 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 230000006023 anti-tumor response Effects 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229950009791 durvalumab Drugs 0.000 description 6
- 230000002519 immonomodulatory effect Effects 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 6
- 208000021937 marginal zone lymphoma Diseases 0.000 description 6
- 210000000822 natural killer cell Anatomy 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 108010087819 Fc receptors Proteins 0.000 description 5
- 102000009109 Fc receptors Human genes 0.000 description 5
- 101001019455 Homo sapiens ICOS ligand Proteins 0.000 description 5
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 5
- 102000003816 Interleukin-13 Human genes 0.000 description 5
- 108090000176 Interleukin-13 Proteins 0.000 description 5
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 description 5
- 230000001270 agonistic effect Effects 0.000 description 5
- 229940034982 antineoplastic agent Drugs 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 210000003162 effector t lymphocyte Anatomy 0.000 description 5
- 201000003444 follicular lymphoma Diseases 0.000 description 5
- 201000005787 hematologic cancer Diseases 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 230000008595 infiltration Effects 0.000 description 5
- 238000001764 infiltration Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 210000003071 memory t lymphocyte Anatomy 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 5
- VDABVNMGKGUPEY-UHFFFAOYSA-N 6-carboxyfluorescein succinimidyl ester Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O VDABVNMGKGUPEY-UHFFFAOYSA-N 0.000 description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- 208000011691 Burkitt lymphomas Diseases 0.000 description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
- 201000002847 Cowden syndrome Diseases 0.000 description 4
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 4
- 102000001398 Granzyme Human genes 0.000 description 4
- 108060005986 Granzyme Proteins 0.000 description 4
- 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 4
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- 108010002616 Interleukin-5 Proteins 0.000 description 4
- 102000000743 Interleukin-5 Human genes 0.000 description 4
- 102100033467 L-selectin Human genes 0.000 description 4
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000005754 cellular signaling Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 230000000139 costimulatory effect Effects 0.000 description 4
- 239000010432 diamond Substances 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 4
- 201000009277 hairy cell leukemia Diseases 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 4
- 102000046492 human ICOSLG Human genes 0.000 description 4
- 239000002955 immunomodulating agent Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 239000007928 intraperitoneal injection Substances 0.000 description 4
- 230000002147 killing effect Effects 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000002794 lymphocyte assay Methods 0.000 description 4
- 210000003563 lymphoid tissue Anatomy 0.000 description 4
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 4
- 230000036210 malignancy Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000000528 statistical test Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 3
- 238000011725 BALB/c mouse Methods 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 3
- 206010011906 Death Diseases 0.000 description 3
- 206010014733 Endometrial cancer Diseases 0.000 description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 description 3
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 3
- 208000036566 Erythroleukaemia Diseases 0.000 description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 3
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 3
- 208000009329 Graft vs Host Disease Diseases 0.000 description 3
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 3
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 3
- 101001117312 Homo sapiens Programmed cell death 1 ligand 2 Proteins 0.000 description 3
- 101000713602 Homo sapiens T-box transcription factor TBX21 Proteins 0.000 description 3
- 102000004388 Interleukin-4 Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 208000007452 Plasmacytoma Diseases 0.000 description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- 206010042971 T-cell lymphoma Diseases 0.000 description 3
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 208000021841 acute erythroid leukemia Diseases 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 229960003852 atezolizumab Drugs 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 230000004186 co-expression Effects 0.000 description 3
- 238000011284 combination treatment Methods 0.000 description 3
- 108091008034 costimulatory receptors Proteins 0.000 description 3
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 201000004101 esophageal cancer Diseases 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 230000003325 follicular Effects 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 208000024908 graft versus host disease Diseases 0.000 description 3
- 230000002489 hematologic effect Effects 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 238000011577 humanized mouse model Methods 0.000 description 3
- 238000011493 immune profiling Methods 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 201000005962 mycosis fungoides Diseases 0.000 description 3
- 206010028537 myelofibrosis Diseases 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000002203 pretreatment Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 230000000284 resting effect Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 201000011549 stomach cancer Diseases 0.000 description 3
- 230000008093 supporting effect Effects 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- 206010044412 transitional cell carcinoma Diseases 0.000 description 3
- 230000036269 ulceration Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 206010069754 Acquired gene mutation Diseases 0.000 description 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 2
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 2
- 201000007815 Bannayan-Riley-Ruvalcaba syndrome Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 208000012609 Cowden disease Diseases 0.000 description 2
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 2
- 206010014967 Ependymoma Diseases 0.000 description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 description 2
- 208000002966 Giant Cell Tumor of Bone Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 2
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 2
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 206010020631 Hypergammaglobulinaemia benign monoclonal Diseases 0.000 description 2
- 101710205775 Inducible T-cell costimulator Proteins 0.000 description 2
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 2
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 2
- 108050003558 Interleukin-17 Proteins 0.000 description 2
- 102000013691 Interleukin-17 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108010092694 L-Selectin Proteins 0.000 description 2
- 102000017578 LAG3 Human genes 0.000 description 2
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 2
- 208000022010 Lhermitte-Duclos disease Diseases 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 2
- 208000000172 Medulloblastoma Diseases 0.000 description 2
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 2
- 208000003445 Mouth Neoplasms Diseases 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 206010067387 Myelodysplastic syndrome transformation Diseases 0.000 description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 208000033755 Neutrophilic Chronic Leukemia Diseases 0.000 description 2
- 101100271175 Oryza sativa subsp. japonica AT10 gene Proteins 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 101710094000 Programmed cell death 1 ligand 1 Proteins 0.000 description 2
- 208000033766 Prolymphocytic Leukemia Diseases 0.000 description 2
- 101710138747 Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 208000009527 Refractory anemia Diseases 0.000 description 2
- 208000033501 Refractory anemia with excess blasts Diseases 0.000 description 2
- 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 description 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 2
- 206010061934 Salivary gland cancer Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 2
- 102100036840 T-box transcription factor TBX21 Human genes 0.000 description 2
- 208000000389 T-cell leukemia Diseases 0.000 description 2
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 108700012920 TNF Proteins 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- 206010047741 Vulval cancer Diseases 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 208000037833 acute lymphoblastic T-cell leukemia Diseases 0.000 description 2
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 2
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- 230000005975 antitumor immune response Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 201000011143 bone giant cell tumor Diseases 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000004970 cd4 cell Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000000432 density-gradient centrifugation Methods 0.000 description 2
- 230000000779 depleting effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000002357 endometrial effect Effects 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 230000004547 gene signature Effects 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000005931 immune cell recruitment Effects 0.000 description 2
- 230000005746 immune checkpoint blockade Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000013115 immunohistochemical detection Methods 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 239000005414 inactive ingredient Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 201000004653 inflammatory breast carcinoma Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 201000000248 mediastinal malignant lymphoma Diseases 0.000 description 2
- 239000011325 microbead Substances 0.000 description 2
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 description 2
- 208000016586 myelodysplastic syndrome with excess blasts Diseases 0.000 description 2
- 210000000581 natural killer T-cell Anatomy 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 208000017805 post-transplant lymphoproliferative disease Diseases 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000009117 preventive therapy Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000000092 prognostic biomarker Substances 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000009465 prokaryotic expression Effects 0.000 description 2
- 125000001500 prolyl group Chemical class [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 208000023933 refractory anemia with excess blasts in transformation Diseases 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000037439 somatic mutation Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 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
- 230000002483 superagonistic effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000011870 unpaired t-test Methods 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 201000005102 vulva cancer Diseases 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical class N1OC=CC=P1 ZZVDXRCAGGQFAK-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
- 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 1
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000023761 AL amyloidosis Diseases 0.000 description 1
- 108010054404 Adenylyl-sulfate kinase Proteins 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 0.000 description 1
- 108090000672 Annexin A5 Proteins 0.000 description 1
- 102000004121 Annexin A5 Human genes 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 101100398412 Arabidopsis thaliana ASK1 gene Proteins 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 210000005236 CD8+ effector T cell Anatomy 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000005024 Castleman disease Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 208000032027 Essential Thrombocythemia Diseases 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000251152 Ginglymostoma cirratum Species 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 101100407305 Homo sapiens CD274 gene Proteins 0.000 description 1
- 101100166600 Homo sapiens CD28 gene Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101100456320 Homo sapiens NR3C2 gene Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101100407307 Homo sapiens PDCD1LG2 gene Proteins 0.000 description 1
- 101000797623 Homo sapiens Protein AMBP Proteins 0.000 description 1
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 1
- 101150118672 ICOS gene Proteins 0.000 description 1
- 101150016644 ICOSLG gene Proteins 0.000 description 1
- 101150034178 ISA3 gene Proteins 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 229940126528 Immuno-Oncology Drug Drugs 0.000 description 1
- 206010053574 Immunoblastic lymphoma Diseases 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
- 102100033461 Interleukin-17A Human genes 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000282842 Lama glama Species 0.000 description 1
- 241000282852 Lama guanicoe Species 0.000 description 1
- 206010024305 Leukaemia monocytic Diseases 0.000 description 1
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 1
- 201000003791 MALT lymphoma Diseases 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 206010060880 Monoclonal gammopathy Diseases 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000002774 Paraproteinemias Diseases 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
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 208000021161 Plasma cell disease Diseases 0.000 description 1
- 241001337451 Polyblastus cancer Species 0.000 description 1
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
- 206010036673 Primary amyloidosis Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 102100032859 Protein AMBP Human genes 0.000 description 1
- 101710186755 Putative pterin-4-alpha-carbinolamine dehydratase 1 Proteins 0.000 description 1
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- 102100039024 Sphingosine kinase 1 Human genes 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 210000000068 Th17 cell Anatomy 0.000 description 1
- 208000005485 Thrombocytosis Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 1
- 229940127174 UCHT1 Drugs 0.000 description 1
- 102000005918 Ubiquitin Thiolesterase Human genes 0.000 description 1
- 108010005656 Ubiquitin Thiolesterase Proteins 0.000 description 1
- 241001416177 Vicugna pacos Species 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001946 anti-microtubular Effects 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical class N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 210000000182 cd11c+cd123- dc Anatomy 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000015861 cell surface binding Effects 0.000 description 1
- 230000023549 cell-cell signaling Effects 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 1
- 208000013056 classic Hodgkin lymphoma Diseases 0.000 description 1
- 238000011198 co-culture assay Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 238000007821 culture assay Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000003145 cytotoxic factor Substances 0.000 description 1
- 231100000050 cytotoxic potential Toxicity 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000004141 diterpene derivatives Chemical class 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000010228 ex vivo assay Methods 0.000 description 1
- 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 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 210000000224 granular leucocyte Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000002871 immunocytoma Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000002434 immunopotentiative effect Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000010212 intracellular staining Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000012804 iterative process Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000002961 luciferase induction Methods 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 208000037524 mixed cellularity Hodgkin lymphoma Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 201000006894 monocytic leukemia Diseases 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001986 peyer's patch Anatomy 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 208000031223 plasma cell leukemia Diseases 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 208000003476 primary myelofibrosis Diseases 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000034223 susceptibility to 2 systemic lupus erythematosus Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940066453 tecentriq Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 201000002510 thyroid cancer Diseases 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
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000004654 triazenes Chemical class 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 208000023747 urothelial carcinoma Diseases 0.000 description 1
- 210000003462 vein Anatomy 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762517309P | 2017-06-09 | 2017-06-09 | |
| US62/517,309 | 2017-06-09 | ||
| US201862666278P | 2018-05-03 | 2018-05-03 | |
| US62/666,278 | 2018-05-03 | ||
| PCT/IB2018/054167 WO2018225033A1 (en) | 2017-06-09 | 2018-06-08 | Combination therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3066048A1 true CA3066048A1 (en) | 2018-12-13 |
Family
ID=62873504
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3066048A Pending CA3066048A1 (en) | 2017-06-09 | 2018-06-08 | Combination therapy |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP3634483A1 (enExample) |
| JP (1) | JP2020522555A (enExample) |
| CN (1) | CN110869049A (enExample) |
| BR (1) | BR112019025325A2 (enExample) |
| CA (1) | CA3066048A1 (enExample) |
| WO (1) | WO2018225033A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116640214A (zh) | 2016-08-09 | 2023-08-25 | 科马布有限公司 | 分离抗体及其应用 |
| GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
| EP3728314A1 (en) | 2017-12-19 | 2020-10-28 | Kymab Limited | Bispecific antibody for icos and pd-l1 |
| AU2021256925A1 (en) * | 2020-04-14 | 2022-11-03 | Ares Trading S.A. | Combination treatment for cancer based upon an ICOS antibody and a PD-L1 antibody TGF-beta-receptor fusion protein |
| CN115698075A (zh) * | 2020-04-14 | 2023-02-03 | 葛兰素史密斯克莱知识产权发展有限公司 | 涉及抗icos和抗pd1抗体，任选地进一步涉及抗tim3抗体的癌症的组合治疗 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57106673A (en) | 1980-12-24 | 1982-07-02 | Chugai Pharmaceut Co Ltd | Dibenzo(b,f)(1,4)oxazepin derivative |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| JP3871503B2 (ja) | 1999-08-30 | 2007-01-24 | 日本たばこ産業株式会社 | 免疫性疾患治療剤 |
| JP4210454B2 (ja) | 2001-03-27 | 2009-01-21 | 日本たばこ産業株式会社 | 炎症性腸疾患治療剤 |
| JP4212278B2 (ja) | 2001-03-01 | 2009-01-21 | 日本たばこ産業株式会社 | 移植片拒絶反応抑制剤 |
| CA2466279A1 (en) | 2001-11-13 | 2003-05-22 | Dana-Farber Cancer Institute, Inc. | Agents that modulate immune cell activation and methods of use thereof |
| AU2003281200A1 (en) | 2002-07-03 | 2004-01-23 | Tasuku Honjo | Immunopotentiating compositions |
| CN101899114A (zh) | 2002-12-23 | 2010-12-01 | 惠氏公司 | 抗pd-1抗体及其用途 |
| EP1591527B1 (en) | 2003-01-23 | 2015-08-26 | Ono Pharmaceutical Co., Ltd. | Substance specific to human pd-1 |
| CN109485727A (zh) | 2005-05-09 | 2019-03-19 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及使用抗pd-1抗体来治疗癌症的方法 |
| KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
| BRPI0811466A2 (pt) | 2007-05-07 | 2014-10-14 | Medimmune Llc | Anticorpo anti-icos isolado, ácido nucleico, vetor, célula isolada, métodos para produzir um anticorpo, para tratar uma doença ou distúrbio, para tratar ou prevenir a rejeição em um paciente de transplante humano, para tratar uma malignidade de célula t em um ser humano, para esgotar células t que expressam icos em um paciente humano, para romper a arquitetura do centro germinal em um órgão linfóide secundário de um primata, para esgotar células b centrais germinais de órgão linfóide secundário de um primata, e para esgotar células b comutadas em classes circulantes em um primata, e, composição farmacêutica. |
| NZ600758A (en) | 2007-06-18 | 2013-09-27 | Merck Sharp & Dohme | Antibodies to human programmed death receptor pd-1 |
| EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
| CA2735006A1 (en) | 2008-08-25 | 2010-03-11 | Amplimmune, Inc. | Pd-1 antagonists and methods of use thereof |
| EP2342228B1 (en) | 2008-09-12 | 2017-09-06 | Oxford University Innovation Limited | Pd-1 specific antibodies and uses thereof |
| EP2342229A1 (en) | 2008-09-12 | 2011-07-13 | ISIS Innovation Limited | Pd-1 specific antibodies and uses thereof |
| ES2592216T3 (es) | 2008-09-26 | 2016-11-28 | Dana-Farber Cancer Institute, Inc. | Anticuerpos anti-PD-1, PD-L1 y PD-L2 humanos y sus usos |
| EP2358392B1 (en) | 2008-11-12 | 2019-01-09 | MedImmune, LLC | Antibody formulation |
| WO2010077634A1 (en) | 2008-12-09 | 2010-07-08 | Genentech, Inc. | Anti-pd-l1 antibodies and their use to enhance t-cell function |
| CA2775761C (en) * | 2009-09-30 | 2018-08-28 | Memorial Sloan-Kettering Cancer Center | Combination immunotherapy for the treatment of cancer |
| US20130017199A1 (en) | 2009-11-24 | 2013-01-17 | AMPLIMMUNE ,Inc. a corporation | Simultaneous inhibition of pd-l1/pd-l2 |
| NZ599405A (en) | 2009-11-24 | 2014-09-26 | Medimmune Ltd | Targeted binding agents against b7-h1 |
| US20110280877A1 (en) | 2010-05-11 | 2011-11-17 | Koji Tamada | Inhibition of B7-H1/CD80 interaction and uses thereof |
| CN101898945B (zh) | 2010-07-27 | 2013-05-08 | 大连理工大学 | 盐析萃取发酵液中丙酮和丁醇的方法 |
| CN106749662B (zh) | 2011-03-31 | 2021-06-18 | 国家医疗保健研究所 | 抗icos的抗体及其用途 |
| AR087405A1 (es) | 2011-08-01 | 2014-03-19 | Genentech Inc | Metodos para tratar el cancer por el uso de antagonistas de union al eje pd-1 e inhibidores de mek |
| EP2785375B1 (en) | 2011-11-28 | 2020-07-22 | Merck Patent GmbH | Anti-pd-l1 antibodies and uses thereof |
| US9856320B2 (en) | 2012-05-15 | 2018-01-02 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting PD-1/PD-L1 signaling |
| SG10201704992SA (en) * | 2012-06-21 | 2017-07-28 | Compugen Ltd | Lsr antibodies, and uses thereof for treatment of cancer |
| ES2684552T3 (es) | 2012-09-03 | 2018-10-03 | Inserm - Institut National De La Santé Et De La Recherche Médicale | Anticuerpos dirigidos contra ICOS para tratar la enfermedad de injerto contra hospedador |
| JP6461800B2 (ja) | 2012-10-04 | 2019-01-30 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | ヒトモノクローナル抗ｐｄ−ｌ１抗体および使用方法 |
| CA2920377A1 (en) * | 2013-08-05 | 2015-02-12 | Cambridge Enterprise Limited | Inhibition of cxcr4 signaling in cancer immunotherapy |
| MA41414A (fr) * | 2015-01-28 | 2017-12-05 | Centre Nat Rech Scient | Protéines de liaison agonistes d' icos |
| RS60614B1 (sr) | 2015-03-23 | 2020-08-31 | Jounce Therapeutics Inc | Antitela za icos |
| US20180230431A1 (en) * | 2015-08-07 | 2018-08-16 | Glaxosmithkline Intellectual Property Development Limited | Combination Therapy |
-
2018
- 2018-06-08 EP EP18739638.7A patent/EP3634483A1/en not_active Withdrawn
- 2018-06-08 JP JP2019567709A patent/JP2020522555A/ja active Pending
- 2018-06-08 CA CA3066048A patent/CA3066048A1/en active Pending
- 2018-06-08 WO PCT/IB2018/054167 patent/WO2018225033A1/en not_active Ceased
- 2018-06-08 BR BR112019025325-4A patent/BR112019025325A2/pt not_active IP Right Cessation
- 2018-06-08 CN CN201880044500.1A patent/CN110869049A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN110869049A (zh) | 2020-03-06 |
| WO2018225033A1 (en) | 2018-12-13 |
| BR112019025325A2 (pt) | 2020-06-23 |
| EP3634483A1 (en) | 2020-04-15 |
| JP2020522555A (ja) | 2020-07-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2022065073A (ja) | Ｂｃｍａ結合分子及びその使用方法 | |
| JP7325959B2 (ja) | 腫瘍特異的細胞の枯渇のための抗ＣＤ２５ ＦＣγ受容体二重特異性抗体 | |
| CA3123420A1 (en) | Bispecific anti-muc16 x anti-cd28 antibodies and uses thereof | |
| KR20190039421A (ko) | 항-tigit 항체, 항-pvrig 항체 및 이들의 조합 | |
| JP7581225B2 (ja) | Ｃｔｌａ－４遮断剤とｐｄ－１遮断剤とを含む抗癌併用療法 | |
| RS65351B1 (sr) | Fc-optimizovana anti-cd25 antitela za tumor-specifičnu depleciju ćelija | |
| CA3066048A1 (en) | Combination therapy | |
| WO2018025221A1 (en) | Anti-icos and anti-pd-1 antibody combination therapy | |
| JP7383620B2 (ja) | 養子細胞療法およびチェックポイント阻害剤を使用する併用療法 | |
| JP2025157343A (ja) | 新規抗体およびＴｒｅｇ枯渇抗体と免疫刺激性抗体との併用 | |
| KR20200140315A (ko) | 항-cd27 항체 및 그의 용도 | |
| KR20220025739A (ko) | T-세포 활성화를 위한 항체 | |
| WO2023285552A1 (en) | Multispecific binding agents against cd40 and cd137 in combination therapy for cancer | |
| US20200181275A1 (en) | Combination therapy with icos agonist and ox40 agonist to treat cancer | |
| US20200190194A1 (en) | Combination therapy | |
| WO2020086476A1 (en) | Dosing | |
| US20200190195A1 (en) | Combination therapy with icos agonist and ox40 agonist to treat cancer | |
| WO2024209072A1 (en) | Multispecific binding agents against pd-l1 and cd137 for treating cancer | |
| TW202540189A (zh) | 在組合療法中能夠結合ｏｘ４０之抗體 | |
| CN117957253A (zh) | 癌症的组合治疗中针对cd40和cd137的多特异性结合剂 | |
| HK40081753A (en) | Antibodies for use in therapy | |
| EA040773B1 (ru) | Анти-tigit антитела, анти-pvrig антитела и их комбинации |