CA3127776A1 - Anticorps diriges contre m(h)dm2/4 et leur utilisation dans le diagnostic et le traitement du cancer - Google Patents
Anticorps diriges contre m(h)dm2/4 et leur utilisation dans le diagnostic et le traitement du cancer Download PDFInfo
- Publication number
- CA3127776A1 CA3127776A1 CA3127776A CA3127776A CA3127776A1 CA 3127776 A1 CA3127776 A1 CA 3127776A1 CA 3127776 A CA3127776 A CA 3127776A CA 3127776 A CA3127776 A CA 3127776A CA 3127776 A1 CA3127776 A1 CA 3127776A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- antibody
- fragment
- amino acid
- acid sequence
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 300
- 201000011510 cancer Diseases 0.000 title claims abstract description 249
- 239000012634 fragment Substances 0.000 claims abstract description 837
- 230000027455 binding Effects 0.000 claims abstract description 187
- 239000000611 antibody drug conjugate Substances 0.000 claims abstract description 76
- 229940049595 antibody-drug conjugate Drugs 0.000 claims abstract description 76
- 229940127089 cytotoxic agent Drugs 0.000 claims abstract description 47
- 239000002254 cytotoxic agent Substances 0.000 claims abstract description 47
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 35
- 206010027476 Metastases Diseases 0.000 claims abstract description 26
- 230000009401 metastasis Effects 0.000 claims abstract description 16
- 238000001727 in vivo Methods 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 574
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 565
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 claims description 401
- 102100032257 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 claims description 388
- 238000000034 method Methods 0.000 claims description 388
- 210000004027 cell Anatomy 0.000 claims description 227
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 138
- 150000001413 amino acids Chemical class 0.000 claims description 97
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims description 57
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims description 57
- 210000000170 cell membrane Anatomy 0.000 claims description 54
- 230000004540 complement-dependent cytotoxicity Effects 0.000 claims description 40
- 108090000623 proteins and genes Proteins 0.000 claims description 36
- 102000004169 proteins and genes Human genes 0.000 claims description 34
- 238000002512 chemotherapy Methods 0.000 claims description 28
- 239000003112 inhibitor Substances 0.000 claims description 28
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical group 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 28
- 229960001592 paclitaxel Drugs 0.000 claims description 27
- 230000002401 inhibitory effect Effects 0.000 claims description 26
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims description 25
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 25
- 108060003951 Immunoglobulin Proteins 0.000 claims description 25
- 230000001472 cytotoxic effect Effects 0.000 claims description 25
- 102000018358 immunoglobulin Human genes 0.000 claims description 25
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 24
- 231100000433 cytotoxic Toxicity 0.000 claims description 24
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 24
- 201000002528 pancreatic cancer Diseases 0.000 claims description 24
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 24
- 108010058566 130-nm albumin-bound paclitaxel Proteins 0.000 claims description 23
- 229960005277 gemcitabine Drugs 0.000 claims description 23
- 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 23
- 230000001965 increasing effect Effects 0.000 claims description 19
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 claims description 16
- 230000005907 cancer growth Effects 0.000 claims description 16
- 230000004044 response Effects 0.000 claims description 16
- 231100000135 cytotoxicity Toxicity 0.000 claims description 15
- 206010009944 Colon cancer Diseases 0.000 claims description 12
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 11
- 230000014509 gene expression Effects 0.000 claims description 11
- 229960005486 vaccine Drugs 0.000 claims description 11
- 230000004544 DNA amplification Effects 0.000 claims description 10
- 208000029742 colonic neoplasm Diseases 0.000 claims description 10
- 230000001419 dependent effect Effects 0.000 claims description 10
- 238000011275 oncology therapy Methods 0.000 claims description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 208000037821 progressive disease Diseases 0.000 claims description 9
- -1 0X40 Proteins 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 8
- 230000004663 cell proliferation Effects 0.000 claims description 8
- 201000005202 lung cancer Diseases 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 208000037819 metastatic cancer Diseases 0.000 claims description 8
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 8
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- 108010077850 Nuclear Localization Signals Proteins 0.000 claims description 7
- 201000001441 melanoma Diseases 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 6
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 6
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 6
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 6
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 5
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 5
- 238000009169 immunotherapy Methods 0.000 claims description 5
- 206010003571 Astrocytoma Diseases 0.000 claims description 4
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 4
- 102000008203 CTLA-4 Antigen Human genes 0.000 claims description 4
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 4
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 claims description 4
- 229930012538 Paclitaxel Natural products 0.000 claims description 4
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 claims description 4
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 230000001093 anti-cancer Effects 0.000 claims description 4
- 238000011503 in vivo imaging Methods 0.000 claims description 4
- 230000003993 interaction Effects 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 108091033319 polynucleotide Proteins 0.000 claims description 3
- 102000040430 polynucleotide Human genes 0.000 claims description 3
- 239000002157 polynucleotide Substances 0.000 claims description 3
- 150000003384 small molecules Chemical class 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims description 2
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 claims description 2
- 102100027314 Beta-2-microglobulin Human genes 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 102100024812 DNA (cytosine-5)-methyltransferase 3A Human genes 0.000 claims description 2
- 108010024491 DNA Methyltransferase 3A Proteins 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 102100030708 GTPase KRas Human genes 0.000 claims description 2
- 101000691214 Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) 50S ribosomal protein L44e Proteins 0.000 claims description 2
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 2
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 2
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 claims description 2
- 101000937544 Homo sapiens Beta-2-microglobulin Proteins 0.000 claims description 2
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 claims description 2
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims description 2
- 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 claims description 2
- 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 claims description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 2
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 claims description 2
- 101000628562 Homo sapiens Serine/threonine-protein kinase STK11 Proteins 0.000 claims description 2
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 claims description 2
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 2
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 2
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 2
- 102000017578 LAG3 Human genes 0.000 claims description 2
- 101150030213 Lag3 gene Proteins 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 108091054455 MAP kinase family Proteins 0.000 claims description 2
- 102000043136 MAP kinase family Human genes 0.000 claims description 2
- 108091007960 PI3Ks Proteins 0.000 claims description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims description 2
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 claims description 2
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 claims description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 2
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 claims description 2
- 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 claims description 2
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 2
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 2
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 claims description 2
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 2
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 208000037842 advanced-stage tumor Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 229960004316 cisplatin Drugs 0.000 claims description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 2
- 229960002949 fluorouracil Drugs 0.000 claims description 2
- 230000002163 immunogen Effects 0.000 claims description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 2
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 2
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 206010041849 Squamous cell carcinoma of the hypopharynx Diseases 0.000 claims 1
- 201000000330 endometrial stromal sarcoma Diseases 0.000 claims 1
- 208000029179 endometrioid stromal sarcoma Diseases 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 238000009097 single-agent therapy Methods 0.000 claims 1
- 206010044412 transitional cell carcinoma Diseases 0.000 claims 1
- 239000000427 antigen Substances 0.000 abstract description 89
- 108091007433 antigens Proteins 0.000 abstract description 89
- 102000036639 antigens Human genes 0.000 abstract description 89
- 230000004614 tumor growth Effects 0.000 abstract description 13
- 239000000562 conjugate Substances 0.000 abstract description 4
- 102100033849 CCHC-type zinc finger nucleic acid binding protein Human genes 0.000 description 467
- 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 description 464
- 235000001014 amino acid Nutrition 0.000 description 121
- 241000699670 Mus sp. Species 0.000 description 49
- 241000699666 Mus <mouse, genus> Species 0.000 description 36
- 239000012528 membrane Substances 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 25
- 101001038388 Glycine max Nodulin-20 Proteins 0.000 description 23
- 101001038410 Medicago truncatula Early nodulin-20 Proteins 0.000 description 23
- 230000000694 effects Effects 0.000 description 22
- 241000283707 Capra Species 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 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 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 15
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 14
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 10
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 10
- 108050005300 MDM4 Proteins 0.000 description 10
- 102000017274 MDM4 Human genes 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000008685 targeting Effects 0.000 description 10
- 238000012217 deletion Methods 0.000 description 9
- 230000037430 deletion Effects 0.000 description 9
- 238000003780 insertion Methods 0.000 description 9
- 230000037431 insertion Effects 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 9
- 238000010172 mouse model Methods 0.000 description 9
- 241001529936 Murinae Species 0.000 description 8
- 238000011374 additional therapy Methods 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 230000003013 cytotoxicity Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 210000000440 neutrophil Anatomy 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 6
- 206010061309 Neoplasm progression Diseases 0.000 description 6
- 108010083101 PNC-27 Proteins 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 210000004443 dendritic cell Anatomy 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- 108010043655 penetratin Proteins 0.000 description 6
- 108091006106 transcriptional activators Proteins 0.000 description 6
- 230000005751 tumor progression Effects 0.000 description 6
- 102000018832 Cytochromes Human genes 0.000 description 5
- 108010052832 Cytochromes Proteins 0.000 description 5
- 108010083196 PNC-28 Proteins 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 108700031196 mouse lisch-like Proteins 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 210000000822 natural killer cell Anatomy 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- OLBRWDOLLRHNOA-VSMYOHOGSA-N pnc-28 Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O)C1=CC=CC=C1 OLBRWDOLLRHNOA-VSMYOHOGSA-N 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108700031308 Antennapedia Homeodomain Proteins 0.000 description 4
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000011533 pre-incubation Methods 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 3
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000011319 anticancer therapy Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000024203 complement activation Effects 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 101150024228 mdm2 gene Proteins 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000002626 targeted therapy Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-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
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000000905 Cadherin Human genes 0.000 description 2
- 108050007957 Cadherin Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 108010078015 Complement C3b Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 101000980354 Homo sapiens Protein Mdm4 Proteins 0.000 description 2
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical group C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 2
- 239000000232 Lipid Bilayer Substances 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 208000009869 Neu-Laxova syndrome Diseases 0.000 description 2
- 102100024314 Protein Mdm4 Human genes 0.000 description 2
- 241000220221 Rosales Species 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 230000030570 cellular localization Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229940126546 immune checkpoint molecule Drugs 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 231100001083 no cytotoxicity Toxicity 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 231100000065 noncytotoxic Toxicity 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 238000012342 propidium iodide staining Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- ALNUHUMOGUVHIO-XXJNWDAFSA-M sodium;7-[(1r,2s)-2-hexyl-5-hydroxycyclopentyl]heptanoate Chemical compound [Na+].CCCCCC[C@H]1CCC(O)[C@@H]1CCCCCCC([O-])=O ALNUHUMOGUVHIO-XXJNWDAFSA-M 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 206010005056 Bladder neoplasm Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- 102000006311 Cyclin D1 Human genes 0.000 description 1
- 102100031051 Cysteine and glycine-rich protein 1 Human genes 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000908058 Homo sapiens Dihydrolipoyl dehydrogenase, mitochondrial Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 238000010824 Kaplan-Meier survival analysis Methods 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 102000001698 Mannose-Binding Lectins Human genes 0.000 description 1
- 108010068997 Mannose-Binding Lectins Proteins 0.000 description 1
- 108090000143 Mouse Proteins Proteins 0.000 description 1
- 101100181396 Mus musculus Laptm5 gene Proteins 0.000 description 1
- 101000980351 Mus musculus Protein Mdm4 Proteins 0.000 description 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 101800001638 Neuromedin-C Proteins 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 241000219492 Quercus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 102100033504 Thyroglobulin Human genes 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000005880 cancer cell killing Effects 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229960000419 catumaxomab Drugs 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000005931 immune cell recruitment Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000030883 malignant astrocytoma Diseases 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 230000002956 necrotizing effect Effects 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 125000005629 sialic acid group Chemical group 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- 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
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
La présente invention concerne, entre autres, certains anticorps anti-M(H)DM2/4 (y compris des anticorps chimériques et humanisés) ou des fragments de liaison à l'antigène de ceux-ci, des compositions pharmaceutiques comprenant des anticorps anti-M(H)DM2/4 ou des fragments de liaison à l'antigène de ceux-ci, des conjugués anticorps-médicament comprenant les anticorps anti-M(H)DM2/4 ou des fragments de liaison à l'antigène de ceux-ci liés à un médicament cytotoxique, et l'utilisation de ces anticorps, fragments, compositions et conjugués pour le traitement du cancer et/ou la prévention de métastases. L'invention concerne, à titre d'exemple, certains anticorps (y compris des anticorps chimériques et humanisés) ou des fragments de liaison à l'antigène de ceux-ci qui se lient de manière spécifique à des épitopes accessibles de manière extracellulaire de M(H)DM2/4 et inhibent la croissance tumorale in vivo, des compositions pharmaceutiques comprenant ces anticorps ou fragments, des conjugués anticorps-médicament comprenant ces anticorps ou fragments, et l'utilisation de ces anticorps, fragments, compositions et conjugués pour le traitement du cancer ou la prévention de métastases.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2019/015900 WO2020159504A1 (fr) | 2019-01-30 | 2019-01-30 | Anticorps dirigés contre m(h)dm2/4 et leur utilisation dans le diagnostic et le traitement du cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3127776A1 true CA3127776A1 (fr) | 2020-08-06 |
Family
ID=65409648
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3127776A Pending CA3127776A1 (fr) | 2019-01-30 | 2019-01-30 | Anticorps diriges contre m(h)dm2/4 et leur utilisation dans le diagnostic et le traitement du cancer |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP3917968A1 (fr) |
| AU (1) | AU2019427766A1 (fr) |
| CA (1) | CA3127776A1 (fr) |
| WO (1) | WO2020159504A1 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3071105A1 (fr) | 2017-07-27 | 2019-01-31 | Nomocan Pharmaceuticals Llc | Anticorps diriges contre m(h)dm2/4 et leur utilisation dans le diagnostic et le traitement du cancer |
| WO2020172115A1 (fr) * | 2019-02-20 | 2020-08-27 | Oncolyze, Inc. | Anticorps anti-hdm2 destiné à être utilisé dans le traitement du cancer |
| WO2023194656A1 (fr) * | 2022-04-08 | 2023-10-12 | Tilt Biotherapeutics Oy | Anticorps monoclonaux pd-l1 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| SG48759A1 (en) | 1990-01-12 | 2002-07-23 | Abgenix Inc | Generation of xenogenic antibodies |
| US5885793A (en) | 1991-12-02 | 1999-03-23 | Medical Research Council | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
| GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
| US5411860A (en) * | 1992-04-07 | 1995-05-02 | The Johns Hopkins University | Amplification of human MDM2 gene in human tumors |
| DE4345249C2 (de) * | 1993-11-19 | 1997-12-11 | Deutsches Krebsforsch | hdm-2-Fragmente mit Bindungsregionen für hdm-2-spezifische Antikörper |
| EP1978033A3 (fr) | 1995-04-27 | 2008-12-24 | Amgen Fremont Inc. | Anticorps humains dérivés à partir de xénosouris immunisée |
| AU2466895A (en) | 1995-04-28 | 1996-11-18 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| FR2738151B1 (fr) * | 1995-09-04 | 1997-09-26 | Rhone Poulenc Rorer Sa | Antagonistes de l'activite oncogenique de la proteine mdm2, et leur utilisation dans le traitement des cancers |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| KR100942002B1 (ko) | 1996-12-03 | 2010-02-12 | 암젠 프레몬트 인코포레이티드 | 복수의 ｖｈ 및 ｖｋ 부위를 함유하는 사람 면역글로불린 유전자좌를 갖는 형질전환된 포유류 및 이로부터 생성된 항체 |
| US7227002B1 (en) | 1997-04-14 | 2007-06-05 | Micromet Ag | Human antibodies that bind human 17-A1/EpCAM tumor antigen |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| MXPA05000511A (es) | 2001-07-12 | 2005-09-30 | Jefferson Foote | Anticuepros super humanizados. |
| WO2010040051A2 (fr) | 2008-10-03 | 2010-04-08 | The Research Foundation Of State University Of New York | Un peptide membranaire résident dans des peptides anticancéreux cause la nécrose de cellules tumorales plutôt que l’apoptose des cellules cancéreuses |
| EP2409712A1 (fr) | 2010-07-19 | 2012-01-25 | International-Drug-Development-Biotech | Anticorps Anti-CD19 doté de fonctions ADCC et CDC et d'un profil de glycosylation amélioré |
| JP2017535528A (ja) * | 2014-10-03 | 2017-11-30 | ノバルティス アーゲー | 組み合わせ治療 |
| US9765117B2 (en) | 2015-08-24 | 2017-09-19 | Romek Figa | Peptides for treating cancer |
| CA3071105A1 (fr) * | 2017-07-27 | 2019-01-31 | Nomocan Pharmaceuticals Llc | Anticorps diriges contre m(h)dm2/4 et leur utilisation dans le diagnostic et le traitement du cancer |
-
2019
- 2019-01-30 AU AU2019427766A patent/AU2019427766A1/en active Pending
- 2019-01-30 CA CA3127776A patent/CA3127776A1/fr active Pending
- 2019-01-30 EP EP19705076.8A patent/EP3917968A1/fr active Pending
- 2019-01-30 WO PCT/US2019/015900 patent/WO2020159504A1/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2020159504A1 (fr) | 2020-08-06 |
| EP3917968A1 (fr) | 2021-12-08 |
| AU2019427766A1 (en) | 2021-09-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10202461B2 (en) | Anti-human TROP-2 antibody having an antitumor activity in vivo | |
| US9670287B2 (en) | Anti-human TROP-2 antibody having anti-tumor activity in vivo | |
| RU2668170C2 (ru) | Анти-в7-н3-антитело | |
| US8017118B2 (en) | Anti-hDlk-1 antibody having an antitumor activity in vivo | |
| US11407840B2 (en) | Antibodies to M(H)DM2/4 and their use in diagnosing and treating cancer | |
| WO2017026497A1 (fr) | Anticorps | |
| CA3127776A1 (fr) | Anticorps diriges contre m(h)dm2/4 et leur utilisation dans le diagnostic et le traitement du cancer | |
| WO2015076425A1 (fr) | Nouvel anticorps monoclonal | |
| US20220098328A1 (en) | Antibodies to m(h)dm2/4 and their use in diagnosing and treating cancer | |
| KR101856904B1 (ko) | Pauf 단백질에 특이적으로 결합하는 항체 및 이의 용도 | |
| NZ716839B2 (en) | Anti-human trop-2 antibody having an antitumor activity in vivo | |
| NZ716839A (en) | Anti-human trop-2 antibody having an antitumor activity in vivo | |
| NZ623464B2 (en) | Anti-human trop-2 antibody having an antitumor activity in vivo |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20240130 |