CA3053348A1 - Radiolabeled anti-lag3 antibodies for immuno-pet imaging - Google Patents
Radiolabeled anti-lag3 antibodies for immuno-pet imaging Download PDFInfo
- Publication number
- CA3053348A1 CA3053348A1 CA3053348A CA3053348A CA3053348A1 CA 3053348 A1 CA3053348 A1 CA 3053348A1 CA 3053348 A CA3053348 A CA 3053348A CA 3053348 A CA3053348 A CA 3053348A CA 3053348 A1 CA3053348 A1 CA 3053348A1
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- lag3
- antigen
- inhibitor
- tumor
- 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
- 238000003384 imaging method Methods 0.000 title claims description 36
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims abstract description 287
- 238000000034 method Methods 0.000 claims abstract description 92
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 claims description 279
- 206010028980 Neoplasm Diseases 0.000 claims description 251
- 230000027455 binding Effects 0.000 claims description 211
- 239000000427 antigen Substances 0.000 claims description 184
- 102000036639 antigens Human genes 0.000 claims description 184
- 108091007433 antigens Proteins 0.000 claims description 184
- 239000012634 fragment Substances 0.000 claims description 157
- 239000003112 inhibitor Substances 0.000 claims description 141
- 239000000562 conjugate Substances 0.000 claims description 74
- 238000002560 therapeutic procedure Methods 0.000 claims description 74
- 229940127121 immunoconjugate Drugs 0.000 claims description 73
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 64
- 238000003556 assay Methods 0.000 claims description 60
- 210000001519 tissue Anatomy 0.000 claims description 56
- 230000000259 anti-tumor effect Effects 0.000 claims description 52
- 210000004027 cell Anatomy 0.000 claims description 48
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 44
- 101100510618 Homo sapiens LAG3 gene Proteins 0.000 claims description 37
- 150000001413 amino acids Chemical group 0.000 claims description 33
- 238000002600 positron emission tomography Methods 0.000 claims description 30
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims description 30
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 28
- 229960000958 deferoxamine Drugs 0.000 claims description 26
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 claims description 25
- 239000000611 antibody drug conjugate Substances 0.000 claims description 25
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 20
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 20
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 20
- 230000004807 localization Effects 0.000 claims description 18
- 230000011664 signaling Effects 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 16
- 239000005557 antagonist Substances 0.000 claims description 16
- 229960004397 cyclophosphamide Drugs 0.000 claims description 16
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 14
- 102000001301 EGF receptor Human genes 0.000 claims description 14
- 108060006698 EGF receptor Proteins 0.000 claims description 14
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 claims description 14
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 claims description 14
- 238000001959 radiotherapy Methods 0.000 claims description 14
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 13
- 102100025082 Melanoma-associated antigen 3 Human genes 0.000 claims description 13
- 108010081667 aflibercept Proteins 0.000 claims description 13
- 201000001441 melanoma Diseases 0.000 claims description 13
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 12
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 12
- 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 claims description 12
- 239000003446 ligand Substances 0.000 claims description 11
- -1 nesvacumab Chemical compound 0.000 claims description 11
- 229960003301 nivolumab Drugs 0.000 claims description 11
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- 239000002246 antineoplastic agent Substances 0.000 claims description 10
- 229960005386 ipilimumab Drugs 0.000 claims description 10
- 229960002621 pembrolizumab Drugs 0.000 claims description 10
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 9
- 229940022399 cancer vaccine Drugs 0.000 claims description 9
- 238000009566 cancer vaccine Methods 0.000 claims description 9
- 238000010494 dissociation reaction Methods 0.000 claims description 9
- 230000005593 dissociations Effects 0.000 claims description 9
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 8
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 8
- 229960002833 aflibercept Drugs 0.000 claims description 8
- 229960003852 atezolizumab Drugs 0.000 claims description 8
- 229950002916 avelumab Drugs 0.000 claims description 8
- 229960004562 carboplatin Drugs 0.000 claims description 8
- 229940127089 cytotoxic agent Drugs 0.000 claims description 8
- 229960003668 docetaxel Drugs 0.000 claims description 8
- 229950009791 durvalumab Drugs 0.000 claims description 8
- 229960004964 temozolomide Drugs 0.000 claims description 8
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 7
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 7
- 102100034608 Angiopoietin-2 Human genes 0.000 claims description 7
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 7
- 239000012275 CTLA-4 inhibitor Substances 0.000 claims description 7
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 7
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 claims description 7
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims description 7
- 108090000172 Interleukin-15 Proteins 0.000 claims description 7
- 108010002350 Interleukin-2 Proteins 0.000 claims description 7
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 claims description 7
- 108010002586 Interleukin-7 Proteins 0.000 claims description 7
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 7
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 7
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 7
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 7
- 239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 7
- 229930012538 Paclitaxel Natural products 0.000 claims description 7
- 229940125555 TIGIT inhibitor Drugs 0.000 claims description 7
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 claims description 7
- 229960005395 cetuximab Drugs 0.000 claims description 7
- 229960004316 cisplatin Drugs 0.000 claims description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 7
- 229960003901 dacarbazine Drugs 0.000 claims description 7
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 7
- 229960000975 daunorubicin Drugs 0.000 claims description 7
- 229960004679 doxorubicin Drugs 0.000 claims description 7
- 229960001433 erlotinib Drugs 0.000 claims description 7
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 7
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 7
- 229960005277 gemcitabine Drugs 0.000 claims description 7
- 108010074108 interleukin-21 Proteins 0.000 claims description 7
- 108040006852 interleukin-4 receptor activity proteins Proteins 0.000 claims description 7
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 claims description 7
- 229960000485 methotrexate Drugs 0.000 claims description 7
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 7
- 229960001156 mitoxantrone Drugs 0.000 claims description 7
- 229950002697 nesvacumab Drugs 0.000 claims description 7
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 7
- 229960001756 oxaliplatin Drugs 0.000 claims description 7
- 229960001592 paclitaxel Drugs 0.000 claims description 7
- 229960000639 pazopanib Drugs 0.000 claims description 7
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 7
- 229960003876 ranibizumab Drugs 0.000 claims description 7
- 229960004641 rituximab Drugs 0.000 claims description 7
- 229950006348 sarilumab Drugs 0.000 claims description 7
- 229960003787 sorafenib Drugs 0.000 claims description 7
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims description 7
- 229960001796 sunitinib Drugs 0.000 claims description 7
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 7
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 7
- 229960004528 vincristine Drugs 0.000 claims description 7
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 7
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 6
- 101710112752 Cytotoxin Proteins 0.000 claims description 6
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims description 6
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims description 6
- 241001467552 Mycobacterium bovis BCG Species 0.000 claims description 6
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 claims description 6
- 229960000397 bevacizumab Drugs 0.000 claims description 6
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 6
- 239000002619 cytotoxin Substances 0.000 claims description 6
- 229950010773 pidilizumab Drugs 0.000 claims description 6
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 5
- 229950003468 dupilumab Drugs 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 4
- 208000018084 Bone neoplasm Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 2
- 206010027406 Mesothelioma Diseases 0.000 claims description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 2
- 201000005787 hematologic cancer Diseases 0.000 claims description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 2
- 210000003494 hepatocyte Anatomy 0.000 claims description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
- 208000015347 renal cell adenocarcinoma Diseases 0.000 claims description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims 2
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims 2
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 claims 2
- 101001005719 Homo sapiens Melanoma-associated antigen 3 Proteins 0.000 claims 2
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims 2
- 230000003127 anti-melanomic effect Effects 0.000 claims 2
- 190000008236 carboplatin Chemical compound 0.000 claims 2
- 108010009583 Transforming Growth Factors Proteins 0.000 claims 1
- 102000009618 Transforming Growth Factors Human genes 0.000 claims 1
- 238000012879 PET imaging Methods 0.000 abstract description 30
- 102000017578 LAG3 Human genes 0.000 abstract description 18
- 125000003275 alpha amino acid group Chemical group 0.000 description 97
- 108090000623 proteins and genes Proteins 0.000 description 45
- 102000004169 proteins and genes Human genes 0.000 description 45
- 235000018102 proteins Nutrition 0.000 description 44
- 230000021615 conjugation Effects 0.000 description 37
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 36
- 235000001014 amino acid Nutrition 0.000 description 35
- 102000043131 MHC class II family Human genes 0.000 description 32
- 108091054438 MHC class II family Proteins 0.000 description 32
- 102000014914 Carrier Proteins Human genes 0.000 description 31
- 108091008324 binding proteins Proteins 0.000 description 31
- 230000000694 effects Effects 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 28
- 229940024606 amino acid Drugs 0.000 description 28
- 239000000872 buffer Substances 0.000 description 27
- 201000011510 cancer Diseases 0.000 description 27
- 239000002738 chelating agent Substances 0.000 description 26
- 238000001574 biopsy Methods 0.000 description 25
- 239000008280 blood Substances 0.000 description 23
- 239000000700 radioactive tracer Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 210000004602 germ cell Anatomy 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 108090000765 processed proteins & peptides Proteins 0.000 description 20
- 241000699666 Mus <mouse, genus> Species 0.000 description 19
- 101150013568 US16 gene Proteins 0.000 description 19
- 210000004369 blood Anatomy 0.000 description 19
- 230000004044 response Effects 0.000 description 19
- 238000006467 substitution reaction Methods 0.000 description 19
- 238000011282 treatment Methods 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 17
- 102000025171 antigen binding proteins Human genes 0.000 description 16
- 108091000831 antigen binding proteins Proteins 0.000 description 16
- 230000004048 modification Effects 0.000 description 16
- 238000012986 modification Methods 0.000 description 16
- 230000035772 mutation Effects 0.000 description 16
- 101150030213 Lag3 gene Proteins 0.000 description 15
- 238000009169 immunotherapy Methods 0.000 description 14
- 238000000163 radioactive labelling Methods 0.000 description 14
- 230000003902 lesion Effects 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 13
- 238000013060 ultrafiltration and diafiltration Methods 0.000 description 13
- 125000000539 amino acid group Chemical group 0.000 description 12
- 230000004614 tumor growth Effects 0.000 description 12
- 102000008096 B7-H1 Antigen Human genes 0.000 description 11
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 11
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 11
- 101710204288 Melanoma-associated antigen 3 Proteins 0.000 description 11
- 206010061218 Inflammation Diseases 0.000 description 10
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 10
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 10
- 238000000684 flow cytometry Methods 0.000 description 10
- 208000015181 infectious disease Diseases 0.000 description 10
- 230000004054 inflammatory process Effects 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 10
- 238000002820 assay format Methods 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 210000000952 spleen Anatomy 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- 108060003951 Immunoglobulin Proteins 0.000 description 8
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 8
- 208000036142 Viral infection Diseases 0.000 description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 8
- 235000018417 cysteine Nutrition 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 8
- 102000018358 immunoglobulin Human genes 0.000 description 8
- 238000002513 implantation Methods 0.000 description 8
- HBAYEVATSBINBX-UHFFFAOYSA-N n-[5-[acetyl(hydroxy)amino]pentyl]-n'-hydroxy-n'-[5-[[4-[hydroxy-[5-[(4-isothiocyanatophenyl)carbamothioylamino]pentyl]amino]-4-oxobutanoyl]amino]pentyl]butanediamide Chemical group CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=S)NC1=CC=C(N=C=S)C=C1 HBAYEVATSBINBX-UHFFFAOYSA-N 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 230000009385 viral infection Effects 0.000 description 8
- 101710144268 B- and T-lymphocyte attenuator Proteins 0.000 description 7
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 7
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 7
- 239000007853 buffer solution Substances 0.000 description 7
- 238000004364 calculation method Methods 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 230000008685 targeting Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 6
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
- 208000035473 Communicable disease Diseases 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 6
- 241000725303 Human immunodeficiency virus Species 0.000 description 6
- 229940125563 LAG3 inhibitor Drugs 0.000 description 6
- 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 6
- 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 description 6
- 102100034256 Mucin-1 Human genes 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 230000008033 biological extinction Effects 0.000 description 6
- 238000003271 compound fluorescence assay Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 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 5
- 108020004414 DNA Proteins 0.000 description 5
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 5
- 241000711549 Hepacivirus C Species 0.000 description 5
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 5
- 101001091538 Homo sapiens Pyruvate kinase PKM Proteins 0.000 description 5
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 5
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 5
- 108010008707 Mucin-1 Proteins 0.000 description 5
- 102100034911 Pyruvate kinase PKM Human genes 0.000 description 5
- 230000006044 T cell activation Effects 0.000 description 5
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 5
- 108091008605 VEGF receptors Proteins 0.000 description 5
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 5
- 102000013127 Vimentin Human genes 0.000 description 5
- 108010065472 Vimentin Proteins 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 230000030741 antigen processing and presentation Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 229940043355 kinase inhibitor Drugs 0.000 description 5
- 238000003468 luciferase reporter gene assay Methods 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 208000021039 metastatic melanoma Diseases 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 150000003384 small molecules Chemical class 0.000 description 5
- 210000005048 vimentin Anatomy 0.000 description 5
- FQIHLPGWBOBPSG-UHFFFAOYSA-N 2-[4,7,10-tris(2-amino-2-oxoethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetamide Chemical compound NC(=O)CN1CCN(CC(N)=O)CCN(CC(N)=O)CCN(CC(N)=O)CC1 FQIHLPGWBOBPSG-UHFFFAOYSA-N 0.000 description 4
- 208000035143 Bacterial infection Diseases 0.000 description 4
- 206010017533 Fungal infection Diseases 0.000 description 4
- 241000700721 Hepatitis B virus Species 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 208000031888 Mycoses Diseases 0.000 description 4
- 239000012270 PD-1 inhibitor Substances 0.000 description 4
- 239000012668 PD-1-inhibitor Substances 0.000 description 4
- 239000012271 PD-L1 inhibitor Substances 0.000 description 4
- 208000030852 Parasitic disease Diseases 0.000 description 4
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 208000022362 bacterial infectious disease Diseases 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000012537 formulation buffer Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 229940121655 pd-1 inhibitor Drugs 0.000 description 4
- 229940121656 pd-l1 inhibitor Drugs 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 3
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 241000713311 Simian immunodeficiency virus Species 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000002591 computed tomography Methods 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 238000011033 desalting Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 238000011577 humanized mouse model Methods 0.000 description 3
- 230000005847 immunogenicity Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000011503 in vivo imaging Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000002601 intratumoral effect Effects 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 238000012636 positron electron tomography Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 210000003289 regulatory T cell Anatomy 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 210000001541 thymus gland Anatomy 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- GLLVIRNJIQOQJW-LDEMJYSLSA-N (z)-5-[3-[5-[3-[[(e)-4-carboxy-3-methylbut-2-enoyl]-oxidoamino]propyl]-8-[3-[[(z)-4-carboxy-3-methylbut-2-enoyl]-oxidoamino]propyl]-11,14-bis(hydroxymethyl)-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexazacyclooctadec-2-yl]propyl-oxidoamino]-3-methyl-5-oxopen Chemical compound [Fe+3].OC(=O)CC(/C)=C\C(=O)N([O-])CCCC1NC(=O)CNC(=O)C(CO)NC(=O)C(CO)NC(=O)C(CCCN([O-])C(=O)\C=C(\C)CC(O)=O)NC(=O)C(CCCN([O-])C(=O)\C=C(/C)CC(O)=O)NC1=O GLLVIRNJIQOQJW-LDEMJYSLSA-N 0.000 description 2
- QBPPRVHXOZRESW-UHFFFAOYSA-N 1,4,7,10-tetraazacyclododecane Chemical compound C1CNCCNCCNCCN1 QBPPRVHXOZRESW-UHFFFAOYSA-N 0.000 description 2
- MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical compound C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 description 2
- JHALWMSZGCVVEM-UHFFFAOYSA-N 2-[4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl]acetic acid Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CC1 JHALWMSZGCVVEM-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 241000235389 Absidia Species 0.000 description 2
- 241000228212 Aspergillus Species 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 241000304886 Bacilli Species 0.000 description 2
- 241000228405 Blastomyces dermatitidis Species 0.000 description 2
- 101100510617 Caenorhabditis elegans sel-8 gene Proteins 0.000 description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 241000606161 Chlamydia Species 0.000 description 2
- 241000193403 Clostridium Species 0.000 description 2
- 241000223205 Coccidioides immitis Species 0.000 description 2
- 241000186227 Corynebacterium diphtheriae Species 0.000 description 2
- 201000007336 Cryptococcosis Diseases 0.000 description 2
- 241000221204 Cryptococcus neoformans Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000224431 Entamoeba Species 0.000 description 2
- 241000498255 Enterobius vermicularis Species 0.000 description 2
- WRFIKQWBKYAFNH-UHFFFAOYSA-N Fusarinine Natural products CC(=C/C(=O)N(O)CCCC(N)C(=O)O)CCO WRFIKQWBKYAFNH-UHFFFAOYSA-N 0.000 description 2
- 101000609762 Gallus gallus Ovalbumin Proteins 0.000 description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 241000228404 Histoplasma capsulatum Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001024703 Homo sapiens Nck-associated protein 5 Proteins 0.000 description 2
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 2
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 2
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 2
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 2
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 241000588748 Klebsiella Species 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- 241000589248 Legionella Species 0.000 description 2
- 208000007764 Legionnaires' Disease Diseases 0.000 description 2
- 241000222722 Leishmania <genus> Species 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 101710092458 Lymphocyte activation gene 3 protein Proteins 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241000235395 Mucor Species 0.000 description 2
- 241000235388 Mucorales Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000186362 Mycobacterium leprae Species 0.000 description 2
- 241000178382 Mycobacterium lepromatosis Species 0.000 description 2
- UIVTVLVVAXJPKM-IJGXQDLJSA-N N',N'',N'''-triacetylfusarinine C Chemical compound O1N2CCC[C@H](NC(C)=O)C(=O)OCC\C(C)=C/C(N(CCC[C@H](NC(C)=O)C(=O)OCC\C(C)=C/C3=[O+]4)O5)=[O+][Fe-3]1451ON3CCC[C@H](NC(=O)C)C(=O)OCC\C(C)=C/C2=[O+]1 UIVTVLVVAXJPKM-IJGXQDLJSA-N 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- 102100036946 Nck-associated protein 5 Human genes 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 241000526686 Paracoccidioides brasiliensis Species 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- 241000224016 Plasmodium Species 0.000 description 2
- 239000004695 Polyether sulfone Substances 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- 241000589516 Pseudomonas Species 0.000 description 2
- 241000235527 Rhizopus Species 0.000 description 2
- 241000606651 Rickettsiales Species 0.000 description 2
- 241000607142 Salmonella Species 0.000 description 2
- 241000242678 Schistosoma Species 0.000 description 2
- 241000607720 Serratia Species 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241001149962 Sporothrix Species 0.000 description 2
- 241000295644 Staphylococcaceae Species 0.000 description 2
- 239000012505 Superdex™ Substances 0.000 description 2
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 241000244031 Toxocara Species 0.000 description 2
- 241000223997 Toxoplasma gondii Species 0.000 description 2
- 241000223109 Trypanosoma cruzi Species 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 241000607626 Vibrio cholerae Species 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 230000006023 anti-tumor response Effects 0.000 description 2
- 229940124350 antibacterial drug Drugs 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000003096 antiparasitic agent Substances 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229940009098 aspartate Drugs 0.000 description 2
- 238000000376 autoradiography Methods 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 238000012754 cardiac puncture Methods 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 2
- 238000004980 dosimetry Methods 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 108700021587 ferrichrome A Proteins 0.000 description 2
- 108010020867 ferrioxamine E Proteins 0.000 description 2
- SRMBQCVUAVULDJ-UHFFFAOYSA-N ferrioxamine b Chemical compound [Fe+3].CC(=O)N([O-])CCCCCNC(=O)CCC(=O)N([O-])CCCCCNC(=O)CCC(=O)N([O-])CCCCCN SRMBQCVUAVULDJ-UHFFFAOYSA-N 0.000 description 2
- MZFKJKOHYACYNT-UHFFFAOYSA-N ferrioxamine e Chemical compound [Fe+3].[O-]N1CCCCCNC(=O)CCC(=O)N([O-])CCCCCNC(=O)CCC(=O)N([O-])CCCCCNC(=O)CCC1=O MZFKJKOHYACYNT-UHFFFAOYSA-N 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 102000048362 human PDCD1 Human genes 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Substances OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 229960003330 pentetic acid Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 2
- 229920006393 polyether sulfone Polymers 0.000 description 2
- 238000011853 postimmunotherapy Methods 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000004627 regenerated cellulose Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 229940118696 vibrio cholerae Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FLCQLSRLQIPNLM-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-acetylsulfanylacetate Chemical compound CC(=O)SCC(=O)ON1C(=O)CCC1=O FLCQLSRLQIPNLM-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 1
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- SYFGLWDDLZQFNI-UHFFFAOYSA-N 2-[4-(carboxymethyl)-1,4,8,11-tetrazabicyclo[6.6.2]hexadecan-11-yl]acetic acid Chemical compound C1CN(CC(O)=O)CCCN2CCN(CC(=O)O)CCCN1CC2 SYFGLWDDLZQFNI-UHFFFAOYSA-N 0.000 description 1
- FSVJFNAIGNNGKK-UHFFFAOYSA-N 2-[cyclohexyl(oxo)methyl]-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one Chemical compound C1C(C2=CC=CC=C2CC2)N2C(=O)CN1C(=O)C1CCCCC1 FSVJFNAIGNNGKK-UHFFFAOYSA-N 0.000 description 1
- FRWYFWZENXDZMU-UHFFFAOYSA-N 2-iodoquinoline Chemical compound C1=CC=CC2=NC(I)=CC=C21 FRWYFWZENXDZMU-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 108010064760 Anidulafungin Proteins 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 229940125565 BMS-986016 Drugs 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- CULUWZNBISUWAS-UHFFFAOYSA-N Benznidazole Chemical compound [O-][N+](=O)C1=NC=CN1CC(=O)NCC1=CC=CC=C1 CULUWZNBISUWAS-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 108010020326 Caspofungin Proteins 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 241000724252 Cucumber mosaic virus Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 108010051539 HLA-DR2 Antigen Proteins 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 description 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 1
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 description 1
- 101000657326 Homo sapiens Protein TANC2 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 102000037978 Immune checkpoint receptors Human genes 0.000 description 1
- 108091008028 Immune checkpoint receptors Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 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
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 0.000 description 1
- 229940125568 MGD013 Drugs 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 108010021062 Micafungin Proteins 0.000 description 1
- 102000007295 Mucin-3 Human genes 0.000 description 1
- 108010008701 Mucin-3 Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100510619 Mus musculus Lag3 gene Proteins 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- ARFHIAQFJWUCFH-IZZDOVSWSA-N Nifurtimox Chemical compound CC1CS(=O)(=O)CCN1\N=C\C1=CC=C([N+]([O-])=O)O1 ARFHIAQFJWUCFH-IZZDOVSWSA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 241001302890 Parachondrostoma toxostoma Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 229920012266 Poly(ether sulfone) PES Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102100034784 Protein TANC2 Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- AQXXZDYPVDOQEE-MXDQRGINSA-N Pyrantel pamoate Chemical compound CN1CCCN=C1\C=C\C1=CC=CS1.C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 AQXXZDYPVDOQEE-MXDQRGINSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- JVHROZDXPAUZFK-UHFFFAOYSA-N TETA Chemical compound OC(=O)CN1CCCN(CC(O)=O)CCN(CC(O)=O)CCCN(CC(O)=O)CC1 JVHROZDXPAUZFK-UHFFFAOYSA-N 0.000 description 1
- 241000244155 Taenia Species 0.000 description 1
- 241000244157 Taenia solium Species 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 229960004748 abacavir Drugs 0.000 description 1
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 231100000987 absorbed dose Toxicity 0.000 description 1
- YQNQNVDNTFHQSW-UHFFFAOYSA-N acetic acid [2-[[(5-nitro-2-thiazolyl)amino]-oxomethyl]phenyl] ester Chemical compound CC(=O)OC1=CC=CC=C1C(=O)NC1=NC=C([N+]([O-])=O)S1 YQNQNVDNTFHQSW-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229960002669 albendazole Drugs 0.000 description 1
- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229960003348 anidulafungin Drugs 0.000 description 1
- JHVAMHSQVVQIOT-MFAJLEFUSA-N anidulafungin Chemical compound C1=CC(OCCCCC)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=O)N[C@@H]2C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N3C[C@H](C)[C@H](O)[C@H]3C(=O)N[C@H](O)[C@H](O)C2)[C@@H](C)O)[C@H](O)[C@@H](O)C=2C=CC(O)=CC=2)[C@@H](C)O)=O)C=C1 JHVAMHSQVVQIOT-MFAJLEFUSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 229960004001 benznidazole Drugs 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229940041011 carbapenems Drugs 0.000 description 1
- JYIKNQVWKBUSNH-WVDDFWQHSA-N caspofungin Chemical compound C1([C@H](O)[C@@H](O)[C@H]2C(=O)N[C@H](C(=O)N3CC[C@H](O)[C@H]3C(=O)N[C@H](NCCN)[C@H](O)C[C@@H](C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N2)[C@@H](C)O)=O)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)[C@H](O)CCN)=CC=C(O)C=C1 JYIKNQVWKBUSNH-WVDDFWQHSA-N 0.000 description 1
- 229960003034 caspofungin Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 150000004697 chelate complex Chemical class 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- ZCIGNRJZKPOIKD-CQXVEOKZSA-N cobicistat Chemical compound S1C(C(C)C)=NC(CN(C)C(=O)N[C@@H](CCN2CCOCC2)C(=O)N[C@H](CC[C@H](CC=2C=CC=CC=2)NC(=O)OCC=2SC=NC=2)CC=2C=CC=CC=2)=C1 ZCIGNRJZKPOIKD-CQXVEOKZSA-N 0.000 description 1
- 229960002402 cobicistat Drugs 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- XXLZPUYGHQWHRN-RPBOFIJWSA-N dehydroemetine Chemical compound COC1=C(OC)C=C2[C@@H]3CC(C[C@@H]4C5=CC(OC)=C(OC)C=C5CCN4)=C(CC)CN3CCC2=C1 XXLZPUYGHQWHRN-RPBOFIJWSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229940029030 dendritic cell vaccine Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229960003061 dihydroemetine Drugs 0.000 description 1
- BDYYDXJSHYEDGB-UHFFFAOYSA-N diloxanide furoate Chemical compound C1=CC(N(C(=O)C(Cl)Cl)C)=CC=C1OC(=O)C1=CC=CO1 BDYYDXJSHYEDGB-UHFFFAOYSA-N 0.000 description 1
- 229960003497 diloxanide furoate Drugs 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- BJAJDJDODCWPNS-UHFFFAOYSA-N dotp Chemical compound O=C1N2CCOC2=NC2=C1SC=C2 BJAJDJDODCWPNS-UHFFFAOYSA-N 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 229960004884 fluconazole Drugs 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- GQZXNSPRSGFJLY-UHFFFAOYSA-N hydroxyphosphanone Chemical compound OP=O GQZXNSPRSGFJLY-UHFFFAOYSA-N 0.000 description 1
- 229940121569 ieramilimab Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 239000003835 ketolide antibiotic agent Substances 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960004525 lopinavir Drugs 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- 229960002159 micafungin Drugs 0.000 description 1
- PIEUQSKUWLMALL-YABMTYFHSA-N micafungin Chemical compound C1=CC(OCCCCC)=CC=C1C1=CC(C=2C=CC(=CC=2)C(=O)N[C@@H]2C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N3C[C@H](C)[C@H](O)[C@H]3C(=O)N[C@H](O)[C@H](O)C2)[C@H](O)CC(N)=O)[C@H](O)[C@@H](O)C=2C=C(OS(O)(=O)=O)C(O)=CC=2)[C@@H](C)O)=O)=NO1 PIEUQSKUWLMALL-YABMTYFHSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229960002644 nifurtimox Drugs 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 229960002480 nitazoxanide Drugs 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000009206 nuclear medicine Methods 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 244000309459 oncolytic virus Species 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- XCGYUJZMCCFSRP-UHFFFAOYSA-N oxamniquine Chemical compound OCC1=C([N+]([O-])=O)C=C2NC(CNC(C)C)CCC2=C1 XCGYUJZMCCFSRP-UHFFFAOYSA-N 0.000 description 1
- 229960000462 oxamniquine Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229960001589 posaconazole Drugs 0.000 description 1
- RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical compound O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 description 1
- 229960002957 praziquantel Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229960000996 pyrantel pamoate Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229940121484 relatlimab Drugs 0.000 description 1
- 238000004153 renaturation Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 229960002814 rilpivirine Drugs 0.000 description 1
- YIBOMRUWOWDFLG-ONEGZZNKSA-N rilpivirine Chemical compound CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-ONEGZZNKSA-N 0.000 description 1
- 229960005560 rindopepimut Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 102000035025 signaling receptors Human genes 0.000 description 1
- 108091005475 signaling receptors Proteins 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 229960004556 tenofovir Drugs 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 1
- MHSKRLJMQQNJNC-UHFFFAOYSA-N terephthalamide Chemical compound NC(=O)C1=CC=C(C(N)=O)C=C1 MHSKRLJMQQNJNC-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229960005053 tinidazole Drugs 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 229940030325 tumor cell vaccine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 1
- 229960004740 voriconazole Drugs 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- QCWXUUIWCKQGHC-YPZZEJLDSA-N zirconium-89 Chemical compound [89Zr] QCWXUUIWCKQGHC-YPZZEJLDSA-N 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1027—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants
- A61K51/1039—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against receptors, cell-surface antigens or cell-surface determinants against T-cell receptors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nuclear Medicine (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762457287P | 2017-02-10 | 2017-02-10 | |
| US62/457,287 | 2017-02-10 | ||
| PCT/US2018/017525 WO2018148476A1 (en) | 2017-02-10 | 2018-02-09 | Radiolabeled anti-lag3 antibodies for immuno-pet imaging |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3053348A1 true CA3053348A1 (en) | 2018-08-16 |
Family
ID=61244834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3053348A Pending CA3053348A1 (en) | 2017-02-10 | 2018-02-09 | Radiolabeled anti-lag3 antibodies for immuno-pet imaging |
Country Status (18)
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI756187B (zh) * | 2015-10-09 | 2022-03-01 | 美商再生元醫藥公司 | 抗ｌａｇ３抗體及其用途 |
| KR102660715B1 (ko) | 2017-02-10 | 2024-04-26 | 리제너론 파마슈티칼스 인코포레이티드 | 면역-pet 이미지화를 위한 방사선 라벨링된 항-lag3 항체 |
| DK3631454T3 (da) | 2017-05-30 | 2023-12-04 | Bristol Myers Squibb Co | Behandling af lag-3 positive tumorer |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| MX2021013815A (es) | 2019-05-13 | 2021-12-14 | Regeneron Pharma | Combinacion de inhibidores de pd-1 e inhibidores de lag-3 para mejorar la eficacia en el tratamiento contra el cancer. |
| KR20210095781A (ko) | 2020-01-24 | 2021-08-03 | 주식회사 에이프릴바이오 | 항원결합 단편 및 생리활성 이펙터 모이어티로 구성된 융합 컨스트럭트를 포함하는 다중결합항체 및 이를 포함하는 약학조성물 |
| IL296372A (en) * | 2020-03-12 | 2022-11-01 | Biond Biologics Ltd | Highly stable anti-shedding materials |
| WO2021262597A2 (en) | 2020-06-22 | 2021-12-30 | Ngm Biopharmaceuticals, Inc. | Lair-1-binding agents and methods of use thereof |
| US12447218B1 (en) * | 2021-02-09 | 2025-10-21 | Actinium Pharmaceuticals, Inc. | Radioconjugates directed to MHC-complexed antigens in cancer |
| CN115337413B (zh) * | 2022-08-08 | 2023-08-22 | 中国科学院近代物理研究所 | 一种针对非小细胞肺癌诊断的放射性分子探针的制备及应用 |
| KR102759386B1 (ko) * | 2022-08-11 | 2025-01-24 | 성균관대학교산학협력단 | 89Zr 표지된 항-CD25 항체를 이용한 immuno-PET |
| EP4665410A1 (en) | 2023-02-17 | 2025-12-24 | Regeneron Pharmaceuticals, Inc. | Radiolabeled anti-lag3 antibodies for immuno-pet imaging |
| WO2024192033A1 (en) | 2023-03-13 | 2024-09-19 | Regeneron Pharmaceuticals, Inc. | Combination of pd-1 inhibitors and lag-3 inhibitors for enhanced efficacy in treating melanoma |
| TW202535926A (zh) * | 2023-10-30 | 2025-09-16 | 美商再生元醫藥公司 | 穩定抗體配製物 |
| WO2025106736A2 (en) | 2023-11-15 | 2025-05-22 | Regeneron Pharmaceuticals, Inc. | Combination of pd-1 inhibitors and lag-3 inhibitors for enhanced efficacy in treating lung cancer |
Family Cites Families (113)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4680338A (en) | 1985-10-17 | 1987-07-14 | Immunomedics, Inc. | Bifunctional linker |
| US5332567A (en) | 1989-08-24 | 1994-07-26 | Immunomedics | Detection and treatment of infections with immunoconjugates |
| FR2656800B1 (fr) | 1990-01-08 | 1992-05-15 | Roussy Inst Gustave | Nouvelles proteines produits par les lymphocytes humains, sequence d'adn codant pour ces proteines et applications pharmaceutiques et biologiques. |
| US5976877A (en) | 1990-01-08 | 1999-11-02 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Proteins produced by human lymphocytes DNA sequence encoding these proteins and their pharmaceutical and biological uses |
| US5428156A (en) | 1993-04-02 | 1995-06-27 | Associated Universities, Inc. | Synthesis of macrocyclic polyaminocarboxylates and their use for preparing stable radiometal antibody immunoconjugates for therapy, spect and pet imaging |
| ZA953629B (en) | 1994-05-06 | 1996-11-05 | Roussy Inst Gustave | Soluble polypeptidic fragments of lag-3 protein method of production thereof therapeutic composition anti-idiotype antibodies |
| JP2000508226A (ja) | 1995-07-21 | 2000-07-04 | アプライド リサーチ システムズ アース ホールディング エヌ．ヴィ． | Ｌａｇ−３タンパク質によるｔｈ１リンパ球を検出、同定、単離並びに選択的に標識およびターゲッティングする方法 |
| US6524802B1 (en) * | 1996-03-29 | 2003-02-25 | The Johns Hopkins University School Of Medicine | Methods of detecting growth differentiation factor-14 |
| EP0900841A1 (en) | 1997-06-18 | 1999-03-10 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | LAG-3 splice variants |
| US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| CA2478011C (en) | 2002-03-01 | 2013-05-21 | Immunomedics, Inc. | Bispecific antibody point mutations for enhancing rate of clearance |
| US9321832B2 (en) * | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| US20040101920A1 (en) | 2002-11-01 | 2004-05-27 | Czeslaw Radziejewski | Modification assisted profiling (MAP) methodology |
| EP1897548B2 (en) | 2003-02-28 | 2024-05-22 | The Johns Hopkins University | T cell regulation |
| KR101076516B1 (ko) | 2003-09-08 | 2011-10-24 | 파나소닉 주식회사 | 플라즈마 처리방법 및 장치 |
| JP5848861B2 (ja) | 2004-04-20 | 2016-01-27 | ジェンマブ エー／エスＧｅｎｍａｂ Ａ／Ｓ | Ｃｄ２０に対するヒトモノクローナル抗体 |
| US20100111856A1 (en) | 2004-09-23 | 2010-05-06 | Herman Gill | Zirconium-radiolabeled, cysteine engineered antibody conjugates |
| WO2006050058A2 (en) | 2004-10-28 | 2006-05-11 | The General Hospital Corporation | Methods of detection and therapy of inflamed tissues using immune modulation |
| US20080193376A1 (en) | 2004-10-28 | 2008-08-14 | The General Hospital Corporation | Methods of Enhanced Detection and Therapy of Inflamed Tissues Using Immune Modulation |
| US8257740B1 (en) | 2011-08-15 | 2012-09-04 | Gp Medical, Inc. | Pharmaceutical composition of nanoparticles |
| US8246995B2 (en) | 2005-05-10 | 2012-08-21 | The Board Of Trustees Of The Leland Stanford Junior University | Hydrophobic nanotubes and nanoparticles as transporters for the delivery of drugs into cells |
| CN101454345B (zh) | 2006-06-02 | 2012-08-08 | 瑞泽恩制药公司 | 人il-6受体的高亲和力抗体 |
| US8889100B2 (en) | 2007-01-11 | 2014-11-18 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
| WO2008124467A1 (en) | 2007-04-06 | 2008-10-16 | Macrocyclics | Bifunctional hydroxamic acid ligands and method of synthesis |
| EP1987839A1 (en) | 2007-04-30 | 2008-11-05 | I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
| US9244059B2 (en) | 2007-04-30 | 2016-01-26 | Immutep Parc Club Orsay | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
| US20090297439A1 (en) | 2008-06-02 | 2009-12-03 | Metheresis Translational Research Sa, | Anti-met monoclonal antibody, fragments and derivatives thereof for use in tumor diagnosis, corresponding compositions and kits |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| WO2010151792A1 (en) | 2009-06-26 | 2010-12-29 | Regeneron Pharmaceuticals, Inc. | Readily isolated bispecific antibodies with native immunoglobulin format |
| WO2011097603A1 (en) | 2010-02-08 | 2011-08-11 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| KR20130098165A (ko) | 2010-06-03 | 2013-09-04 | 제넨테크, 인크. | 항체 및 면역접합체의 이뮤노-ｐｅｔ 영상화 및 그의 용도 |
| TWI589589B (zh) | 2010-12-20 | 2017-07-01 | 建南德克公司 | 抗間皮素（ｍｅｓｏｔｈｅｌｉｎ）抗體及免疫接合物 |
| SI3865581T1 (sl) | 2011-08-05 | 2024-12-31 | Regeneron Pharmaceuticals, Inc. | Miši s humanizirano univerzalno lahko verigo |
| EP2800587A2 (en) | 2012-01-06 | 2014-11-12 | LinXis B.V. | Method for preparing cell targeting conjugates, and the complexes obtained |
| WO2013138696A1 (en) | 2012-03-16 | 2013-09-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Zirconium-89 complexes, methods of labeling cells, labeled cells, kits, and methods of use thereof |
| AR090549A1 (es) | 2012-03-30 | 2014-11-19 | Genentech Inc | Anticuerpos anti-lgr5 e inmunoconjugados |
| EP2844300B1 (en) | 2012-05-01 | 2018-10-17 | Genentech, Inc. | Anti-pmel17 antibodies and immunoconjugates |
| AR091098A1 (es) | 2012-05-21 | 2015-01-14 | Genentech Inc | ANTICUERPOS E INMUNOCONJUGADOS CONTRA Ly6E Y METODOS DE USO |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
| WO2014025828A1 (en) | 2012-08-06 | 2014-02-13 | The Regents Of The University Of California | Engineered antibody fragments for targeting and imaging cd8 expression in vivo |
| JOP20200236A1 (ar) | 2012-09-21 | 2017-06-16 | Regeneron Pharma | الأجسام المضادة لمضاد cd3 وجزيئات ربط الأنتيجين ثنائية التحديد التي تربط cd3 وcd20 واستخداماتها |
| US20150246146A1 (en) | 2012-10-25 | 2015-09-03 | Life Technologies Corporation | Methods and compositions for enzyme-mediated site-specific radiolabeling of glycoproteins |
| EP2740726A1 (en) | 2012-12-07 | 2014-06-11 | 3B Pharmaceuticals GmbH | Neurotensin receptor ligands |
| TWI682941B (zh) | 2013-02-01 | 2020-01-21 | 美商再生元醫藥公司 | 含嵌合恆定區之抗體 |
| EP3339327A3 (en) | 2013-02-28 | 2018-09-19 | National Cancer Center | Antibody against insoluble fibrin |
| CN105163765A (zh) | 2013-03-13 | 2015-12-16 | 伊麦吉纳博公司 | 与cd8的抗原结合构建体 |
| PE20151672A1 (es) | 2013-03-14 | 2015-11-27 | Genentech Inc | Anticuerpos e inmunoconjugados anti-b7-h4 |
| WO2014159087A1 (en) | 2013-03-14 | 2014-10-02 | The Board Of Trustees Of The Leland Stanford Junior University | Radiolabeled anti-glypican-3 immunoconjugates for immuno-pet imaging of hepatocellular carcinoma |
| IL240838B (en) * | 2013-03-15 | 2022-09-01 | Glaxosmithkline Ip Dev Ltd | Anti-3–lag binding proteins |
| WO2014200969A2 (en) | 2013-06-10 | 2014-12-18 | Millennium Pharmaceuticals, Inc. | Methods of treatment of cancer |
| AR096687A1 (es) | 2013-06-24 | 2016-01-27 | Genentech Inc | Anticuerpos anti-fcrh5 |
| FR3008408B1 (fr) | 2013-07-11 | 2018-03-09 | Mc Saf | Nouveaux conjugues anticorps-medicament et leur utilisation en therapie |
| RS62189B1 (sr) | 2013-08-26 | 2021-08-31 | Biontech Research And Development Inc | Nukleinske kiseline koje kodiraju humana antitela na sijalil-luis a |
| RS64268B1 (sr) | 2013-09-20 | 2023-07-31 | Bristol Myers Squibb Co | Kombinacija anti-lag-3 antitela i anti-pd-1 antitela za lečenje tumora |
| EP3049442A4 (en) | 2013-09-26 | 2017-06-28 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
| JP6707445B2 (ja) | 2013-10-21 | 2020-06-10 | ジェネンテック， インコーポレイテッド | 抗Ｌｙ６Ｅ抗体及び使用方法 |
| CN105980404B (zh) | 2013-11-19 | 2021-01-12 | 弗雷达克斯有限责任公司 | 人源化抗激肽释放酶-2抗体 |
| SG11201604784XA (en) | 2013-12-13 | 2016-07-28 | Genentech Inc | Anti-cd33 antibodies and immunoconjugates |
| GB201322626D0 (en) | 2013-12-19 | 2014-02-05 | Immutep S A | Combined preparations for the treatment of cancer |
| TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗ｐｄ-ｌ１之人類抗體 |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| GB201403875D0 (en) | 2014-03-05 | 2014-04-16 | Cantargia Ab | Novel antibodies and uses thereof |
| MY178160A (en) * | 2014-03-11 | 2020-10-06 | Regeneron Pharma | Anti-egfrviii antibodies and uses thereof |
| UY36032A (es) | 2014-03-14 | 2015-10-30 | Novartis Ag | Moléculas de anticuerpo que se unen a lag-3 y usos de las mismas |
| WO2015140212A1 (en) | 2014-03-19 | 2015-09-24 | Universität Zürich | Multidentate bifunctional chelating agents for radionuclide complexation in diagnostics and therapy |
| KR20170003582A (ko) | 2014-05-22 | 2017-01-09 | 제넨테크, 인크. | 항-gpc3 항체 및 면역접합체 |
| WO2015188934A1 (en) | 2014-06-10 | 2015-12-17 | 3B Pharmaceuticals Gmbh | Conjugate comprising a neurotensin receptor ligand and use thereof |
| EP2954933A1 (en) | 2014-06-10 | 2015-12-16 | 3B Pharmaceuticals GmbH | Conjugate comprising a neurotensin receptor ligand |
| EP3155015A1 (en) | 2014-06-11 | 2017-04-19 | F. Hoffmann-La Roche AG | Anti-lgr5 antibodies and uses thereof |
| TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
| GB201413913D0 (en) | 2014-08-06 | 2014-09-17 | Cantargia Ab | Novel antibodies and uses thereof |
| PT3177640T (pt) | 2014-08-08 | 2020-08-31 | Univ Leland Stanford Junior | Agentes pd-1 de alta afinidade e métodos de utilização |
| JO3663B1 (ar) | 2014-08-19 | 2020-08-27 | Merck Sharp & Dohme | الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين |
| CN106804108B (zh) | 2014-09-12 | 2021-08-10 | 基因泰克公司 | 抗-b7-h4抗体及免疫缀合物 |
| SG11201701623UA (en) | 2014-09-12 | 2017-03-30 | Genentech Inc | Anti-her2 antibodies and immunoconjugates |
| PE20170670A1 (es) | 2014-09-12 | 2017-06-06 | Genentech Inc | Anticuerpos anti-cll-1 e inmunoconjugados |
| JP6689836B2 (ja) | 2014-10-16 | 2020-04-28 | ザ ユニバーシティー オブ メルボルンＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ ｏｆ Ｍｅｌｂｏｕｒｎｅ | 新規なイメージング組成物およびその使用 |
| EP3702367B1 (en) | 2014-11-25 | 2024-05-15 | Bristol-Myers Squibb Company | Novel pd-l1 binding polypeptides for imaging |
| MA41463A (fr) | 2015-02-03 | 2017-12-12 | Anaptysbio Inc | Anticorps dirigés contre le gène d'activation 3 des lymphocytes (lag-3) |
| EP4252784A3 (en) | 2015-03-06 | 2024-01-10 | Mayo Foundation for Medical Education and Research | Methods for cell labeling and medical imaging |
| NL2014423B1 (en) | 2015-03-09 | 2016-10-13 | Linxis B V | Method for removing weakly bound functional moieties from cell targeting conjugates. |
| EP3285809B1 (en) | 2015-04-20 | 2019-09-11 | eFFECTOR Therapeutics, Inc. | Inhibitors of immune checkpoint modulators for use in treating cancer and infections |
| TWI773646B (zh) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | 結合lag-3的分子和其使用方法 |
| CN108348601B (zh) * | 2015-07-22 | 2022-05-17 | 索伦托药业有限公司 | 与lag3结合的抗体治疗剂 |
| CN106699888B (zh) | 2015-07-28 | 2020-11-06 | 上海昀怡健康科技发展有限公司 | 一种pd-1抗体及其制备方法和应用 |
| US20170097333A1 (en) | 2015-09-28 | 2017-04-06 | Merck Sharp & Dohme Corp. | Cell based assay to measure the t-cell stimulating capacity of anti-lag3 antibodies and other agents |
| EP4218833A1 (en) | 2015-10-01 | 2023-08-02 | Whitehead Institute for Biomedical Research | Labeling of antibodies |
| TWI756187B (zh) | 2015-10-09 | 2022-03-01 | 美商再生元醫藥公司 | 抗ｌａｇ３抗體及其用途 |
| KR102220275B1 (ko) | 2015-11-18 | 2021-02-26 | 머크 샤프 앤드 돔 코포레이션 | Pd1 및/또는 lag3 결합제 |
| WO2017087826A1 (en) | 2015-11-18 | 2017-05-26 | Memorial Sloan Kettering Cancer Center | Systems, methods, and compositions for imaging androgen receptor axis activity in carcinoma, and related therapeutic compositions and methods |
| US20190330336A1 (en) | 2015-11-19 | 2019-10-31 | Sutro Biopharma, Inc. | Anti-lag3 antibodies, compositions comprising anti-lag3 antibodies and methods of making and using anti-lag3 antibodies |
| AU2016371639A1 (en) | 2015-12-16 | 2018-06-28 | Merck Sharp & Dohme Llc | Anti-LAG3 antibodies and antigen-binding fragments |
| SG10201601719RA (en) | 2016-03-04 | 2017-10-30 | Agency Science Tech & Res | Anti-LAG-3 Antibodies |
| UA127200C2 (uk) | 2016-05-18 | 2023-06-07 | Бьорінгер Інгельхайм Інтернаціональ Гмбх | Молекула антитіла до pd1 |
| CN109414514B (zh) | 2016-05-19 | 2022-03-11 | 百时美施贵宝公司 | Pet成像免疫调节剂 |
| WO2017213494A1 (en) | 2016-06-06 | 2017-12-14 | Linxis B.V. | Cell targeting conjugates |
| AU2017283181B2 (en) | 2016-06-20 | 2024-08-15 | F-Star Therapeutics Limited | Binding molecules binding PD-L1 and LAG-3 |
| KR102497259B1 (ko) | 2016-06-23 | 2023-02-07 | 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드 | Ｌａｇ―３ 항체, 이의 항원-결합 단편 및 이의 약학적 용도 |
| US11179484B2 (en) | 2016-06-24 | 2021-11-23 | University Of Iowa Research Foundation | Compositions and methods of treating melanoma |
| EP3266465A1 (en) | 2016-07-06 | 2018-01-10 | Julius-Maximilians-Universität Würzburg | Immune complexes |
| US11633506B2 (en) | 2016-07-18 | 2023-04-25 | Wisconsin Alumni Research Foundation | Using targeted radiotherapy (TRT) to drive anti-tumor immune response to immunotherapies |
| WO2018017526A1 (en) | 2016-07-18 | 2018-01-25 | Wisconsin Alumni Research Foundation | Radiohalogenated agents for in situ immune modulated cancer vaccination |
| WO2018049083A1 (en) | 2016-09-07 | 2018-03-15 | The Regents Of The University Of California | Antibodies to oxidation-specific epitopes |
| HRP20231281T1 (hr) * | 2016-09-23 | 2024-02-02 | Regeneron Pharmaceuticals, Inc. | Bispecifična anti-muc16-cd3 antitijela i konjugati anti-muc16 s lijekom |
| WO2018058125A1 (en) | 2016-09-26 | 2018-03-29 | Ensemble Group Holdings | Methods of assessing and treating cancer in subjects having dysregulated lymphatic systems |
| US11103603B2 (en) | 2016-10-20 | 2021-08-31 | The University Of North Carolina At Chapel Hill | 18F-labeled compounds for PET imaging and uses thereof |
| EP3565555A4 (en) | 2016-11-07 | 2021-03-17 | VIDAC Pharma Ltd. | USE OF HEXOKINASE 2 / MITOCHONDRIA DETACHMENT COMPOUNDS FOR THE TREATMENT OF HEXOKINASE 2 (HK2) EXPRESSING CANCERS |
| IL266917B2 (en) * | 2016-11-29 | 2023-10-01 | Regeneron Pharma | Anti-human prolactin receptor (prlr) antibody-drug conjugates and use thereof in combination therapy of prlr positive breast cancer |
| JP7105235B2 (ja) * | 2016-12-01 | 2022-07-22 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 免疫ｐｅｔイメージングのための放射性標識された抗ｐｄ－ｌ１抗体 |
| AU2017371498B2 (en) | 2016-12-09 | 2020-10-01 | Regeneron Pharmaceuticals, Inc. | Systems and methods for sequencing T cell receptors and uses thereof |
| KR102660715B1 (ko) * | 2017-02-10 | 2024-04-26 | 리제너론 파마슈티칼스 인코포레이티드 | 면역-pet 이미지화를 위한 방사선 라벨링된 항-lag3 항체 |
| CN111133115A (zh) | 2017-09-20 | 2020-05-08 | 瑞泽恩制药公司 | 用于其肿瘤携带高过客基因突变负荷的患者的免疫治疗方法 |
-
2018
- 2018-02-09 KR KR1020197026079A patent/KR102660715B1/ko active Active
- 2018-02-09 CA CA3053348A patent/CA3053348A1/en active Pending
- 2018-02-09 BR BR112019016336-0A patent/BR112019016336A2/pt unknown
- 2018-02-09 AU AU2018219909A patent/AU2018219909B2/en active Active
- 2018-02-09 US US15/892,440 patent/US10905784B2/en active Active
- 2018-02-09 MX MX2019009565A patent/MX2019009565A/es unknown
- 2018-02-09 IL IL313695A patent/IL313695A/en unknown
- 2018-02-09 EA EA201991673A patent/EA201991673A1/ru unknown
- 2018-02-09 MA MA047456A patent/MA47456A/fr unknown
- 2018-02-09 MA MA46814A patent/MA46814B2/fr unknown
- 2018-02-09 CN CN201880024346.1A patent/CN110650974B/zh active Active
- 2018-02-09 CN CN202410383516.2A patent/CN118557758A/zh active Pending
- 2018-02-09 IL IL268667A patent/IL268667B2/en unknown
- 2018-02-09 SG SG11201907208XA patent/SG11201907208XA/en unknown
- 2018-02-09 WO PCT/US2018/017525 patent/WO2018148476A1/en not_active Ceased
- 2018-02-09 KR KR1020247013269A patent/KR102813603B1/ko active Active
- 2018-02-09 JP JP2019543051A patent/JP7167041B2/ja active Active
- 2018-02-09 EP EP18706165.0A patent/EP3580238A1/en active Pending
- 2018-02-09 MY MYPI2019004493A patent/MY200034A/en unknown
-
2019
- 2019-08-08 PH PH12019501837A patent/PH12019501837A1/en unknown
- 2019-08-09 MX MX2025004620A patent/MX2025004620A/es unknown
- 2019-08-09 CL CL2019002264A patent/CL2019002264A1/es unknown
- 2019-08-09 CO CO2019008675A patent/CO2019008675A2/es unknown
-
2020
- 2020-12-18 US US17/127,618 patent/US11511001B2/en active Active
-
2022
- 2022-10-25 US US18/049,609 patent/US20230270894A1/en active Pending
-
2025
- 2025-02-11 AU AU2025200923A patent/AU2025200923A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11511001B2 (en) | Radiolabeled anti-LAG3 antibodies for immuno-PET imaging | |
| US12077587B2 (en) | Anti-CD8 antibodies and uses thereof | |
| US12053534B2 (en) | Radiolabeled anti-PD-L1 antibodies for immuno-PET imaging | |
| EP4665410A1 (en) | Radiolabeled anti-lag3 antibodies for immuno-pet imaging | |
| EA043673B1 (ru) | Меченные радиоактивным изотопом антитела к lag3 для иммуно-пэт-визуализации | |
| EA044824B1 (ru) | Антитела к cd8 и пути их применения |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220811 |
|
| EEER | Examination request |
Effective date: 20220811 |
|
| EEER | Examination request |
Effective date: 20220811 |
|
| EEER | Examination request |
Effective date: 20220811 |
|
| EEER | Examination request |
Effective date: 20220811 |