CA3065836A1 - Agents for cancer therapy or prophylaxis and uses therefor - Google Patents
Agents for cancer therapy or prophylaxis and uses therefor Download PDFInfo
- Publication number
- CA3065836A1 CA3065836A1 CA3065836A CA3065836A CA3065836A1 CA 3065836 A1 CA3065836 A1 CA 3065836A1 CA 3065836 A CA3065836 A CA 3065836A CA 3065836 A CA3065836 A CA 3065836A CA 3065836 A1 CA3065836 A1 CA 3065836A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- antigen
- polypeptide
- rankl
- amino acid
- 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
- 238000011321 prophylaxis Methods 0.000 title description 4
- 238000011275 oncology therapy Methods 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 164
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 142
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims abstract description 121
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims abstract description 121
- 229940126546 immune checkpoint molecule Drugs 0.000 claims abstract description 117
- 239000005557 antagonist Substances 0.000 claims abstract description 108
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 43
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 27
- 239000003446 ligand Substances 0.000 claims abstract description 21
- 238000011161 development Methods 0.000 claims abstract description 16
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 208000037819 metastatic cancer Diseases 0.000 claims abstract description 10
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims abstract description 10
- 230000027455 binding Effects 0.000 claims description 576
- 238000009739 binding Methods 0.000 claims description 576
- 239000000427 antigen Substances 0.000 claims description 571
- 102000036639 antigens Human genes 0.000 claims description 570
- 108091007433 antigens Proteins 0.000 claims description 570
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 176
- 239000012634 fragment Substances 0.000 claims description 170
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 164
- 229920001184 polypeptide Polymers 0.000 claims description 161
- 150000001413 amino acids Chemical group 0.000 claims description 126
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 claims description 98
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 74
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 71
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 63
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 61
- 235000001014 amino acid Nutrition 0.000 claims description 57
- 201000011510 cancer Diseases 0.000 claims description 51
- 229960001251 denosumab Drugs 0.000 claims description 49
- 229940124044 RANKL antagonist Drugs 0.000 claims description 48
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 47
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 42
- 229960003301 nivolumab Drugs 0.000 claims description 40
- 108090000623 proteins and genes Proteins 0.000 claims description 38
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 33
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 33
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 31
- 230000001394 metastastic effect Effects 0.000 claims description 30
- 102000004169 proteins and genes Human genes 0.000 claims description 30
- -1 tactile (CD96) Proteins 0.000 claims description 29
- 108060003951 Immunoglobulin Proteins 0.000 claims description 27
- 102000018358 immunoglobulin Human genes 0.000 claims description 27
- 229960003852 atezolizumab Drugs 0.000 claims description 24
- 229950002916 avelumab Drugs 0.000 claims description 23
- 229950009791 durvalumab Drugs 0.000 claims description 22
- 229960002621 pembrolizumab Drugs 0.000 claims description 22
- 229950010773 pidilizumab Drugs 0.000 claims description 21
- 229950007217 tremelimumab Drugs 0.000 claims description 21
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 19
- 229960005386 ipilimumab Drugs 0.000 claims description 17
- 201000001441 melanoma Diseases 0.000 claims description 15
- 102100025221 CD70 antigen Human genes 0.000 claims description 13
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 claims description 13
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 13
- 102000050627 Glucocorticoid-Induced TNFR-Related Human genes 0.000 claims description 12
- 229940124060 PD-1 antagonist Drugs 0.000 claims description 12
- 229940123751 PD-L1 antagonist Drugs 0.000 claims description 12
- 102100029740 Poliovirus receptor Human genes 0.000 claims description 12
- 101710187882 Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims description 12
- 108010048507 poliovirus receptor Proteins 0.000 claims description 12
- 206010009944 Colon cancer Diseases 0.000 claims description 11
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 claims description 11
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 claims description 11
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 10
- 206010060862 Prostate cancer Diseases 0.000 claims description 10
- 101150051188 Adora2a gene Proteins 0.000 claims description 9
- 101150078577 Adora2b gene Proteins 0.000 claims description 9
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 9
- 101710144268 B- and T-lymphocyte attenuator Proteins 0.000 claims description 9
- 102100038077 CD226 antigen Human genes 0.000 claims description 9
- 108010046080 CD27 Ligand Proteins 0.000 claims description 9
- 102100038078 CD276 antigen Human genes 0.000 claims description 9
- 102100027816 Cytotoxic and regulatory T-cell molecule Human genes 0.000 claims description 9
- 102100031351 Galectin-9 Human genes 0.000 claims description 9
- 101710121810 Galectin-9 Proteins 0.000 claims description 9
- 102100035943 HERV-H LTR-associating protein 2 Human genes 0.000 claims description 9
- 101000884298 Homo sapiens CD226 antigen Proteins 0.000 claims description 9
- 101001021491 Homo sapiens HERV-H LTR-associating protein 2 Proteins 0.000 claims description 9
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 claims description 9
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 claims description 9
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 claims description 9
- 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 claims description 9
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 claims description 9
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims description 9
- 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 claims description 9
- 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 claims description 9
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 claims description 9
- 239000002246 antineoplastic agent Substances 0.000 claims description 9
- 108010082808 4-1BB Ligand Proteins 0.000 claims description 8
- HFOBENSCBRZVSP-LKXGYXEUSA-N C[C@@H](O)[C@H](NC(=O)N[C@@H](CC(N)=O)c1nc(no1)[C@@H](N)CO)C(O)=O Chemical compound C[C@@H](O)[C@H](NC(=O)N[C@@H](CC(N)=O)c1nc(no1)[C@@H](N)CO)C(O)=O HFOBENSCBRZVSP-LKXGYXEUSA-N 0.000 claims description 8
- 101000764622 Homo sapiens Transmembrane and immunoglobulin domain-containing protein 2 Proteins 0.000 claims description 8
- RRMJMHOQSALEJJ-UHFFFAOYSA-N N-[5-[[4-[4-[(dimethylamino)methyl]-3-phenylpyrazol-1-yl]pyrimidin-2-yl]amino]-4-methoxy-2-morpholin-4-ylphenyl]prop-2-enamide Chemical compound CN(C)CC=1C(=NN(C=1)C1=NC(=NC=C1)NC=1C(=CC(=C(C=1)NC(C=C)=O)N1CCOCC1)OC)C1=CC=CC=C1 RRMJMHOQSALEJJ-UHFFFAOYSA-N 0.000 claims description 8
- 102100026224 Transmembrane and immunoglobulin domain-containing protein 2 Human genes 0.000 claims description 8
- 102100026890 Tumor necrosis factor ligand superfamily member 4 Human genes 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 208000014018 liver neoplasm Diseases 0.000 claims description 8
- 230000002829 reductive effect Effects 0.000 claims description 8
- 229940066453 tecentriq Drugs 0.000 claims description 8
- 101150013553 CD40 gene Proteins 0.000 claims description 7
- 101000884279 Homo sapiens CD276 antigen Proteins 0.000 claims description 7
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 7
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 7
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 7
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 7
- 102100022464 5'-nucleotidase Human genes 0.000 claims description 6
- 102100036008 CD48 antigen Human genes 0.000 claims description 6
- 101000716130 Homo sapiens CD48 antigen Proteins 0.000 claims description 6
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 claims description 6
- 102100034980 ICOS ligand Human genes 0.000 claims description 6
- 102100035488 Nectin-2 Human genes 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 6
- 108010072917 class-I restricted T cell-associated molecule Proteins 0.000 claims description 6
- 206010017758 gastric cancer Diseases 0.000 claims description 6
- 229950007213 spartalizumab Drugs 0.000 claims description 6
- 201000011549 stomach cancer Diseases 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 5
- 101710141230 Natural killer cell receptor 2B4 Proteins 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 5
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 5
- 230000002519 immonomodulatory effect Effects 0.000 claims description 5
- 230000001771 impaired effect Effects 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
- 230000004043 responsiveness Effects 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 108010029697 CD40 Ligand Proteins 0.000 claims description 4
- 102100032937 CD40 ligand Human genes 0.000 claims description 4
- 108010038940 CD48 Antigen Proteins 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 claims description 4
- 101000764263 Homo sapiens Tumor necrosis factor ligand superfamily member 4 Proteins 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 4
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 239000003550 marker Substances 0.000 claims description 4
- 108091006084 receptor activators Proteins 0.000 claims description 4
- 206010038038 rectal cancer Diseases 0.000 claims description 4
- 201000001275 rectum cancer Diseases 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 206010061424 Anal cancer Diseases 0.000 claims description 3
- 101710185679 CD276 antigen Proteins 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 101710167716 Cytotoxic and regulatory T-cell molecule Proteins 0.000 claims description 3
- 206010014733 Endometrial cancer Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 claims description 3
- 101001019455 Homo sapiens ICOS ligand Proteins 0.000 claims description 3
- 101710093458 ICOS ligand Proteins 0.000 claims description 3
- 102000053646 Inducible T-Cell Co-Stimulator Human genes 0.000 claims description 3
- 108700013161 Inducible T-Cell Co-Stimulator Proteins 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- 101710098610 Leukocyte surface antigen CD47 Proteins 0.000 claims description 3
- 206010027480 Metastatic malignant melanoma Diseases 0.000 claims description 3
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 3
- 206010057644 Testis cancer Diseases 0.000 claims description 3
- 206010047741 Vulval cancer Diseases 0.000 claims description 3
- 201000007538 anal carcinoma Diseases 0.000 claims description 3
- 210000003445 biliary tract Anatomy 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- 229940127089 cytotoxic agent Drugs 0.000 claims description 3
- 230000002357 endometrial effect Effects 0.000 claims description 3
- 230000003511 endothelial effect Effects 0.000 claims description 3
- 201000004101 esophageal cancer Diseases 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 239000003966 growth inhibitor Substances 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 230000002440 hepatic effect Effects 0.000 claims description 3
- 208000021039 metastatic melanoma Diseases 0.000 claims description 3
- 208000030940 penile carcinoma Diseases 0.000 claims description 3
- 201000008174 penis carcinoma Diseases 0.000 claims description 3
- 230000019491 signal transduction Effects 0.000 claims description 3
- 201000003120 testicular cancer Diseases 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- 208000012991 uterine carcinoma Diseases 0.000 claims description 3
- 201000005102 vulva cancer Diseases 0.000 claims description 3
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims description 2
- 206010061934 Salivary gland cancer Diseases 0.000 claims description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 claims 6
- 108010043610 KIR Receptors Proteins 0.000 claims 4
- 102000002698 KIR Receptors Human genes 0.000 claims 4
- 108010042215 OX40 Ligand Proteins 0.000 claims 4
- 102100022203 Tumor necrosis factor receptor superfamily member 25 Human genes 0.000 claims 4
- 101710187740 Tumor necrosis factor receptor superfamily member 25 Proteins 0.000 claims 4
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 claims 4
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 claims 4
- 241001367053 Autographa gamma Species 0.000 claims 2
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 claims 2
- 206010055113 Breast cancer metastatic Diseases 0.000 claims 1
- 206010055114 Colon cancer metastatic Diseases 0.000 claims 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 claims 1
- 206010050017 Lung cancer metastatic Diseases 0.000 claims 1
- 206010063916 Metastatic gastric cancer Diseases 0.000 claims 1
- 206010066882 Metastatic salivary gland cancer Diseases 0.000 claims 1
- 206010063569 Metastatic squamous cell carcinoma Diseases 0.000 claims 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 22
- 125000003275 alpha amino acid group Chemical group 0.000 description 117
- 210000004027 cell Anatomy 0.000 description 113
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 90
- 102100028787 Tumor necrosis factor receptor superfamily member 11A Human genes 0.000 description 64
- 101710178436 Tumor necrosis factor receptor superfamily member 11A Proteins 0.000 description 59
- 241000699670 Mus sp. Species 0.000 description 57
- 238000007912 intraperitoneal administration Methods 0.000 description 57
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 51
- 229940024606 amino acid Drugs 0.000 description 47
- 230000014509 gene expression Effects 0.000 description 39
- 238000007920 subcutaneous administration Methods 0.000 description 31
- 238000011282 treatment Methods 0.000 description 30
- 150000007523 nucleic acids Chemical group 0.000 description 28
- 238000011081 inoculation Methods 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 27
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 26
- 230000035772 mutation Effects 0.000 description 21
- 238000001543 one-way ANOVA Methods 0.000 description 21
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 20
- 108091028043 Nucleic acid sequence Proteins 0.000 description 20
- 230000004614 tumor growth Effects 0.000 description 20
- 239000013598 vector Substances 0.000 description 19
- 108020004414 DNA Proteins 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 18
- 230000006870 function Effects 0.000 description 18
- 102000048362 human PDCD1 Human genes 0.000 description 18
- 230000004927 fusion Effects 0.000 description 17
- 230000000875 corresponding effect Effects 0.000 description 16
- 230000000670 limiting effect Effects 0.000 description 16
- 125000005647 linker group Chemical group 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- 229940125565 BMS-986016 Drugs 0.000 description 14
- 238000011740 C57BL/6 mouse Methods 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 229950004270 enoblituzumab Drugs 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 101000830603 Homo sapiens Tumor necrosis factor ligand superfamily member 11 Proteins 0.000 description 13
- 210000004443 dendritic cell Anatomy 0.000 description 13
- 238000000375 direct analysis in real time Methods 0.000 description 13
- 238000012063 dual-affinity re-targeting Methods 0.000 description 13
- 102000053529 human TNFSF11 Human genes 0.000 description 13
- 210000004072 lung Anatomy 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- 241000894007 species Species 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 230000003993 interaction Effects 0.000 description 12
- 231100000205 reproductive and developmental toxicity Toxicity 0.000 description 12
- 230000018109 developmental process Effects 0.000 description 11
- 102000048776 human CD274 Human genes 0.000 description 11
- 102000043321 human CTLA4 Human genes 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 102000039446 nucleic acids Human genes 0.000 description 10
- 108020004707 nucleic acids Proteins 0.000 description 10
- 210000003289 regulatory T cell Anatomy 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 108091026890 Coding region Proteins 0.000 description 9
- 101000648503 Homo sapiens Tumor necrosis factor receptor superfamily member 11A Proteins 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000012642 immune effector Substances 0.000 description 9
- 230000036039 immunity Effects 0.000 description 9
- 229940121354 immunomodulator Drugs 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 8
- 102000001708 Protein Isoforms Human genes 0.000 description 8
- 108010029485 Protein Isoforms Proteins 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 210000000987 immune system Anatomy 0.000 description 8
- 229940072221 immunoglobulins Drugs 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 238000010186 staining Methods 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 7
- 230000021615 conjugation Effects 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 238000000684 flow cytometry Methods 0.000 description 7
- 238000005734 heterodimerization reaction Methods 0.000 description 7
- 210000000265 leukocyte Anatomy 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 230000003211 malignant effect Effects 0.000 description 7
- 238000009097 single-agent therapy Methods 0.000 description 7
- 230000008685 targeting Effects 0.000 description 7
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 6
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- 102000014128 RANK Ligand Human genes 0.000 description 6
- 108010025832 RANK Ligand Proteins 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 230000003190 augmentative effect Effects 0.000 description 6
- 239000000090 biomarker Substances 0.000 description 6
- 238000002648 combination therapy Methods 0.000 description 6
- 239000003431 cross linking reagent Substances 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 230000009977 dual effect Effects 0.000 description 6
- 210000003162 effector t lymphocyte Anatomy 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 102000017578 LAG3 Human genes 0.000 description 5
- 101150030213 Lag3 gene Proteins 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 230000003042 antagnostic effect Effects 0.000 description 5
- 102000053530 human TNFRSF11A Human genes 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 229950011263 lirilumab Drugs 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 210000002997 osteoclast Anatomy 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 4
- 102000002627 4-1BB Ligand Human genes 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 241000699800 Cricetinae Species 0.000 description 4
- 239000004971 Cross linker Substances 0.000 description 4
- 206010062016 Immunosuppression Diseases 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 238000012313 Kruskal-Wallis test Methods 0.000 description 4
- 101000830602 Mus musculus Tumor necrosis factor ligand superfamily member 11 Proteins 0.000 description 4
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 4
- 210000005006 adaptive immune system Anatomy 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 238000003018 immunoassay Methods 0.000 description 4
- 230000001506 immunosuppresive effect Effects 0.000 description 4
- 238000009169 immunotherapy Methods 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 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 4
- 239000000463 material Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 201000001514 prostate carcinoma Diseases 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- ZADWXFSZEAPBJS-SNVBAGLBSA-N (2r)-2-amino-3-(1-methylindol-3-yl)propanoic acid Chemical compound C1=CC=C2N(C)C=C(C[C@@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-SNVBAGLBSA-N 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- 238000011725 BALB/c mouse Methods 0.000 description 3
- 101100476210 Caenorhabditis elegans rnt-1 gene Proteins 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 3
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 3
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 3
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 3
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 3
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 3
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 3
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 3
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 3
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 3
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108010027767 Rank-Fc Proteins 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 150000001345 alkine derivatives Chemical class 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 102000006815 folate receptor Human genes 0.000 description 3
- 108020005243 folate receptor Proteins 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000000833 heterodimer Substances 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000000683 nonmetastatic effect Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000000392 somatic effect Effects 0.000 description 3
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000011870 unpaired t-test Methods 0.000 description 3
- 210000005167 vascular cell Anatomy 0.000 description 3
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 3
- 229910052727 yttrium Inorganic materials 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
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
- YPBKTZBXSBLTDK-PKNBQFBNSA-N (3e)-3-[(3-bromo-4-fluoroanilino)-nitrosomethylidene]-4-[2-(sulfamoylamino)ethylamino]-1,2,5-oxadiazole Chemical compound NS(=O)(=O)NCCNC1=NON\C1=C(N=O)/NC1=CC=C(F)C(Br)=C1 YPBKTZBXSBLTDK-PKNBQFBNSA-N 0.000 description 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- GJXCLGKEGAGUQC-UHFFFAOYSA-N 3-[(3-amino-3-oxopropyl)disulfanyl]propanamide Chemical compound NC(=O)CCSSCCC(N)=O GJXCLGKEGAGUQC-UHFFFAOYSA-N 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 108091007065 BIRCs Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 102100033620 Calponin-1 Human genes 0.000 description 2
- 241000283153 Cetacea Species 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 241000251730 Chondrichthyes Species 0.000 description 2
- 101800001467 Envelope glycoprotein E2 Proteins 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 241001272567 Hominoidea Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 2
- 101100407305 Homo sapiens CD274 gene Proteins 0.000 description 2
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 2
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 2
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 2
- 102000037977 Immune checkpoint ligands Human genes 0.000 description 2
- 108091008029 Immune checkpoint ligands Proteins 0.000 description 2
- 102000037978 Immune checkpoint receptors Human genes 0.000 description 2
- 108091008028 Immune checkpoint receptors Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 102100022338 Integrin alpha-M Human genes 0.000 description 2
- 241000270322 Lepidosauria Species 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- 241001436793 Meru Species 0.000 description 2
- 206010027452 Metastases to bone Diseases 0.000 description 2
- 206010027458 Metastases to lung Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- YGACXVRLDHEXKY-WXRXAMBDSA-N O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 Chemical compound O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 YGACXVRLDHEXKY-WXRXAMBDSA-N 0.000 description 2
- 241001504519 Papio ursinus Species 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108010038036 Receptor Activator of Nuclear Factor-kappa B Proteins 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 241000282695 Saimiri Species 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 101800001271 Surface protein Proteins 0.000 description 2
- 108700012920 TNF Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 102100024568 Tumor necrosis factor ligand superfamily member 11 Human genes 0.000 description 2
- 101710097161 Tumor necrosis factor ligand superfamily member 11 Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000010170 biological method Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 239000002771 cell marker Substances 0.000 description 2
- 238000012412 chemical coupling Methods 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229950006370 epacadostat Drugs 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 2
- 239000000710 homodimer Substances 0.000 description 2
- 230000004727 humoral immunity Effects 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229950009034 indoximod Drugs 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 210000005007 innate immune system Anatomy 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 230000001926 lymphatic effect Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000012474 protein marker Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 208000034223 susceptibility to 2 systemic lupus erythematosus Diseases 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- TYKASZBHFXBROF-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(2,5-dioxopyrrol-1-yl)acetate Chemical compound O=C1CCC(=O)N1OC(=O)CN1C(=O)C=CC1=O TYKASZBHFXBROF-UHFFFAOYSA-N 0.000 description 1
- XUDGDVPXDYGCTG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-[2-(2,5-dioxopyrrolidin-1-yl)oxycarbonyloxyethylsulfonyl]ethyl carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCCS(=O)(=O)CCOC(=O)ON1C(=O)CCC1=O XUDGDVPXDYGCTG-UHFFFAOYSA-N 0.000 description 1
- JKHVDAUOODACDU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCN1C(=O)C=CC1=O JKHVDAUOODACDU-UHFFFAOYSA-N 0.000 description 1
- PVGATNRYUYNBHO-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(2,5-dioxopyrrol-1-yl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O PVGATNRYUYNBHO-UHFFFAOYSA-N 0.000 description 1
- BQWBEDSJTMWJAE-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[(2-iodoacetyl)amino]benzoate Chemical compound C1=CC(NC(=O)CI)=CC=C1C(=O)ON1C(=O)CCC1=O BQWBEDSJTMWJAE-UHFFFAOYSA-N 0.000 description 1
- GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 1
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 description 1
- MVQNJLJLEGZFGP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-benzoylbenzoate Chemical compound C=1C=C(C(=O)C=2C=CC=CC=2)C=CC=1C(=O)ON1C(=O)CCC1=O MVQNJLJLEGZFGP-UHFFFAOYSA-N 0.000 description 1
- VLARLSIGSPVYHX-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-(2,5-dioxopyrrol-1-yl)hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O VLARLSIGSPVYHX-UHFFFAOYSA-N 0.000 description 1
- WCMOHMXWOOBVMZ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCN1C(=O)C=CC1=O WCMOHMXWOOBVMZ-UHFFFAOYSA-N 0.000 description 1
- QYEAAMBIUQLHFQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 QYEAAMBIUQLHFQ-UHFFFAOYSA-N 0.000 description 1
- IHVODYOQUSEYJJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)C(CC1)CCC1CN1C(=O)C=CC1=O IHVODYOQUSEYJJ-UHFFFAOYSA-N 0.000 description 1
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 1
- LTDQGCFMTVHZKP-UHFFFAOYSA-N (4-bromophenyl)-(4,6-dimethoxy-3-methyl-1-benzofuran-2-yl)methanone Chemical compound O1C2=CC(OC)=CC(OC)=C2C(C)=C1C(=O)C1=CC=C(Br)C=C1 LTDQGCFMTVHZKP-UHFFFAOYSA-N 0.000 description 1
- FMSYGGOEIOBUOR-UHFFFAOYSA-N (4-isothiocyanatophenyl)-phenylmethanone Chemical compound C=1C=C(N=C=S)C=CC=1C(=O)C1=CC=CC=C1 FMSYGGOEIOBUOR-UHFFFAOYSA-N 0.000 description 1
- FCUUVMMUABUNMK-UHFFFAOYSA-N 1,2,5-oxadiazole-3-carboximidamide Chemical compound NC(=N)C=1C=NON=1 FCUUVMMUABUNMK-UHFFFAOYSA-N 0.000 description 1
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
- QWQORQURWIFIRD-UHFFFAOYSA-N 1-(4-benzoylphenyl)pyrrolidine-2,5-dione Chemical compound C=1C=C(N2C(CCC2=O)=O)C=CC=1C(=O)C1=CC=CC=C1 QWQORQURWIFIRD-UHFFFAOYSA-N 0.000 description 1
- OJQSISYVGFJJBY-UHFFFAOYSA-N 1-(4-isocyanatophenyl)pyrrole-2,5-dione Chemical compound C1=CC(N=C=O)=CC=C1N1C(=O)C=CC1=O OJQSISYVGFJJBY-UHFFFAOYSA-N 0.000 description 1
- UFFVWIGGYXLXPC-UHFFFAOYSA-N 1-[2-(2,5-dioxopyrrol-1-yl)phenyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C1=CC=CC=C1N1C(=O)C=CC1=O UFFVWIGGYXLXPC-UHFFFAOYSA-N 0.000 description 1
- SGVWDRVQIYUSRA-UHFFFAOYSA-N 1-[2-[2-(2,5-dioxopyrrol-1-yl)ethyldisulfanyl]ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CCSSCCN1C(=O)C=CC1=O SGVWDRVQIYUSRA-UHFFFAOYSA-N 0.000 description 1
- DIYPCWKHSODVAP-UHFFFAOYSA-N 1-[3-(2,5-dioxopyrrol-1-yl)benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 DIYPCWKHSODVAP-UHFFFAOYSA-N 0.000 description 1
- VOTJUWBJENROFB-UHFFFAOYSA-N 1-[3-[[3-(2,5-dioxo-3-sulfopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoyloxy]-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)C(S(O)(=O)=O)CC1=O VOTJUWBJENROFB-UHFFFAOYSA-N 0.000 description 1
- CULQNACJHGHAER-UHFFFAOYSA-N 1-[4-[(2-iodoacetyl)amino]benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=C(NC(=O)CI)C=C1 CULQNACJHGHAER-UHFFFAOYSA-N 0.000 description 1
- ASNTZYQMIUCEBV-UHFFFAOYSA-N 2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ASNTZYQMIUCEBV-UHFFFAOYSA-N 0.000 description 1
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- NITXODYAMWZEJY-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanehydrazide Chemical compound NNC(=O)CCSSC1=CC=CC=N1 NITXODYAMWZEJY-UHFFFAOYSA-N 0.000 description 1
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 description 1
- ZMRMMAOBSFSXLN-UHFFFAOYSA-N 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanehydrazide Chemical compound C1=CC(CCCC(=O)NN)=CC=C1N1C(=O)C=CC1=O ZMRMMAOBSFSXLN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IOJFHZXQSLNAQJ-UHFFFAOYSA-N 4-azido-2,3,5,6-tetrafluorobenzoic acid Chemical compound OC(=O)C1=C(F)C(F)=C(N=[N+]=[N-])C(F)=C1F IOJFHZXQSLNAQJ-UHFFFAOYSA-N 0.000 description 1
- YELWNIMQOUETBV-UHFFFAOYSA-N 4-azido-2-hydroxy-n-[2-(pyridin-2-yldisulfanyl)ethyl]benzamide Chemical compound OC1=CC(N=[N+]=[N-])=CC=C1C(=O)NCCSSC1=CC=CC=N1 YELWNIMQOUETBV-UHFFFAOYSA-N 0.000 description 1
- QLHLYJHNOCILIT-UHFFFAOYSA-N 4-o-(2,5-dioxopyrrolidin-1-yl) 1-o-[2-[4-(2,5-dioxopyrrolidin-1-yl)oxy-4-oxobutanoyl]oxyethyl] butanedioate Chemical compound O=C1CCC(=O)N1OC(=O)CCC(=O)OCCOC(=O)CCC(=O)ON1C(=O)CCC1=O QLHLYJHNOCILIT-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- BYXHQQCXAJARLQ-ZLUOBGJFSA-N Ala-Ala-Ala Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O BYXHQQCXAJARLQ-ZLUOBGJFSA-N 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 101150014003 Batf3 gene Proteins 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 101100463133 Caenorhabditis elegans pdl-1 gene Proteins 0.000 description 1
- 241000288951 Callithrix <genus> Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 description 1
- 241000251556 Chordata Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 241001125840 Coryphaenidae Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000000579 Epigen Human genes 0.000 description 1
- 108010016906 Epigen Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 208000001382 Experimental Melanoma Diseases 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010008177 Fd immunoglobulins Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000002966 Giant Cell Tumor of Bone Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101001099381 Homo sapiens Peroxisomal biogenesis factor 19 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 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
- 241000283953 Lagomorpha Species 0.000 description 1
- 241000283986 Lepus Species 0.000 description 1
- WMFYOYKPJLRMJI-UHFFFAOYSA-N Lercanidipine hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 WMFYOYKPJLRMJI-UHFFFAOYSA-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
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000721578 Melopsittacus Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 108010077854 Natural Killer Cell Receptors Proteins 0.000 description 1
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 101710116886 P-loop GTPase Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010056995 Perforin Proteins 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 102100038883 Peroxisomal biogenesis factor 19 Human genes 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 240000004713 Pisum sativum Species 0.000 description 1
- 235000010582 Pisum sativum Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000010498 Receptor Activator of Nuclear Factor-kappa B Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000288959 Saguinus Species 0.000 description 1
- 241000288961 Saguinus imperator Species 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 241000287231 Serinus Species 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 101000588258 Taenia solium Paramyosin Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 102000018594 Tumour necrosis factor Human genes 0.000 description 1
- 108050007852 Tumour necrosis factor Proteins 0.000 description 1
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 1
- 108091005906 Type I transmembrane proteins Proteins 0.000 description 1
- 208000006593 Urologic Neoplasms Diseases 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- XRICQUGWKQNRNJ-UHFFFAOYSA-N [2-(2,5-dioxopyrrolidin-1-yl)acetyl]sulfanyl acetate Chemical compound CC(=O)OSC(=O)CN1C(=O)CCC1=O XRICQUGWKQNRNJ-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 108010017893 alanyl-alanyl-alanine Proteins 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- FMIALDTXQFBRKH-YVPNKAGPSA-N alpha-NeupAc-(2->8)-alpha-NeupAc-(2->3)-beta-D-Galp Chemical compound O1[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(=O)C)[C@@H](O)C[C@@]1(C(O)=O)O[C@H](CO)[C@@H](O)[C@H]1[C@H](NC(C)=O)[C@@H](O)C[C@@](C(O)=O)(O[C@H]2[C@H]([C@@H](CO)O[C@@H](O)[C@@H]2O)O)O1 FMIALDTXQFBRKH-YVPNKAGPSA-N 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000005911 anti-cytotoxic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000123 anti-resoprtive effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 201000003286 autosomal recessive osteopetrosis 7 Diseases 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 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
- VYLDEYYOISNGST-UHFFFAOYSA-N bissulfosuccinimidyl suberate Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)C(S(O)(=O)=O)CC1=O VYLDEYYOISNGST-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 201000011143 bone giant cell tumor Diseases 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011220 combination immunotherapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000010276 construction Methods 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
- 230000001461 cytolytic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- CEJLBZWIKQJOAT-UHFFFAOYSA-N dichloroisocyanuric acid Chemical compound ClN1C(=O)NC(=O)N(Cl)C1=O CEJLBZWIKQJOAT-UHFFFAOYSA-N 0.000 description 1
- ASXBYYWOLISCLQ-HZYVHMACSA-N dihydrostreptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](CO)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O ASXBYYWOLISCLQ-HZYVHMACSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- IYBKWXQWKPSYDT-UHFFFAOYSA-L ethylene glycol disuccinate bis(sulfo-N-succinimidyl) ester sodium salt Chemical compound [Na+].[Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCC(=O)OCCOC(=O)CCC(=O)ON1C(=O)C(S([O-])(=O)=O)CC1=O IYBKWXQWKPSYDT-UHFFFAOYSA-L 0.000 description 1
- YOMFVLRTMZWACQ-UHFFFAOYSA-N ethyltrimethylammonium Chemical compound CC[N+](C)(C)C YOMFVLRTMZWACQ-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000011985 exploratory data analysis Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 102000048770 human CD276 Human genes 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000005746 immune checkpoint blockade Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- MJRDGTVDJKACQZ-VKHMYHEASA-N l-photo-leucine Chemical compound OC(=O)[C@@H](N)CC1(C)N=N1 MJRDGTVDJKACQZ-VKHMYHEASA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000005296 lymph node development Effects 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 210000003810 lymphokine-activated killer cell Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000005741 malignant process Effects 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000023247 mammary gland development Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000001483 mobilizing effect Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- QFEQUQOYWKZOOV-UHFFFAOYSA-N n-(3-azidopropyl)-2-iodoacetamide Chemical compound ICC(=O)NCCCN=[N+]=[N-] QFEQUQOYWKZOOV-UHFFFAOYSA-N 0.000 description 1
- YCRUVTMZPHEOAM-UHFFFAOYSA-N n-hex-5-ynyl-2-iodoacetamide Chemical compound ICC(=O)NCCCCC#C YCRUVTMZPHEOAM-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 101710135378 pH 6 antigen Proteins 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229920000889 poly(m-phenylene isophthalamide) Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- MKNJJMHQBYVHRS-UHFFFAOYSA-M sodium;1-[11-(2,5-dioxopyrrol-1-yl)undecanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCCCCCCN1C(=O)C=CC1=O MKNJJMHQBYVHRS-UHFFFAOYSA-M 0.000 description 1
- ULARYIUTHAWJMU-UHFFFAOYSA-M sodium;1-[4-(2,5-dioxopyrrol-1-yl)butanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O ULARYIUTHAWJMU-UHFFFAOYSA-M 0.000 description 1
- VUFNRPJNRFOTGK-UHFFFAOYSA-M sodium;1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 VUFNRPJNRFOTGK-UHFFFAOYSA-M 0.000 description 1
- MIDXXTLMKGZDPV-UHFFFAOYSA-M sodium;1-[6-(2,5-dioxopyrrol-1-yl)hexanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O MIDXXTLMKGZDPV-UHFFFAOYSA-M 0.000 description 1
- RPENMORRBUTCPR-UHFFFAOYSA-M sodium;1-hydroxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].ON1C(=O)CC(S([O-])(=O)=O)C1=O RPENMORRBUTCPR-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 231100000617 superantigen Toxicity 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2875—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 NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
-
- 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
- C07K16/2878—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 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- 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
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2017902125 | 2017-06-05 | ||
| AU2017902125A AU2017902125A0 (en) | 2017-06-05 | "Agents for cancer therapy or prophylaxis and uses therefor" | |
| PCT/AU2018/050557 WO2018223182A1 (en) | 2017-06-05 | 2018-06-05 | A combination of, or a bispecific binding molecule to, an immune checkpoint molecule antagonist and a rank-l (nf- kb ligand) antagonist for cancer therapy or prophylaxis and uses therefor. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3065836A1 true CA3065836A1 (en) | 2018-12-13 |
Family
ID=64565634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3065836A Pending CA3065836A1 (en) | 2017-06-05 | 2018-06-05 | Agents for cancer therapy or prophylaxis and uses therefor |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20230042913A1 (enExample) |
| EP (1) | EP3634484A4 (enExample) |
| JP (1) | JP2020522529A (enExample) |
| CN (1) | CN111032085A (enExample) |
| AU (1) | AU2018280340A1 (enExample) |
| CA (1) | CA3065836A1 (enExample) |
| WO (1) | WO2018223182A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3037380A1 (en) | 2016-10-11 | 2018-04-19 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
| JP2022514215A (ja) * | 2018-12-05 | 2022-02-10 | ザ カウンシル オブ ザ クイーンズランド インスティテュート オブ メディカル リサーチ | Ｒａｎｋアンタゴニストおよびその使用 |
| KR20220008253A (ko) * | 2019-01-03 | 2022-01-20 | 엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔 (인쎄름) | 암을 앓는 대상에서 cd8+ t 세포 의존성 면역 반응을 향상시키기 위한 방법 및 약학적 조성물 |
| CN110179977A (zh) * | 2019-05-22 | 2019-08-30 | 华中科技大学同济医学院附属同济医院 | 用于治疗黑色素瘤、肺癌或结直肠癌的组合药物制剂 |
| WO2020252329A1 (en) * | 2019-06-14 | 2020-12-17 | The Scripps Research Institute | Immune checkpoint blocking bispecific molecules |
| US20220267467A1 (en) * | 2019-07-19 | 2022-08-25 | WuXi Biologics Ireland Limited | Polypeptide complex for conjugation and use thereof |
| CN110938652A (zh) * | 2019-11-07 | 2020-03-31 | 浙江大学医学院附属第一医院 | 打靶载体及构建白喉毒素调控清除巨噬细胞的f4/80-dtr转基因小鼠的方法和应用 |
| WO2021115465A1 (en) * | 2019-12-13 | 2021-06-17 | Biosion Inc. | Antibodies binding rankl and uses thereof |
| MX2022007840A (es) * | 2019-12-27 | 2022-07-19 | Chugai Pharmaceutical Co Ltd | Anticuerpo anti antigeno-4 asociado al linfocito t citotoxico (ctla4) y uso del mismo. |
| SE544001C2 (en) * | 2020-03-17 | 2021-10-26 | Xbrane Biopharma Ab | Novel combination of tis sequences, signal peptide sequences and nucleic acid sequences encoding heavy and light chains of an antibody |
| SE544000C2 (en) * | 2020-03-17 | 2021-10-26 | Xbrane Biopharma Ab | Novel combination of tis sequence, signal peptide sequence and nucleic acid sequence encoding a recombinant protein |
| CN111808198B (zh) * | 2020-07-27 | 2022-06-03 | 广东安普泽生物医药股份有限公司 | 一种特异性结合rankl靶向治疗药物的抗体及其应用 |
| TW202305009A (zh) * | 2021-04-08 | 2023-02-01 | 美商默沙東有限責任公司 | 以皮下投予抗pd1抗體治療癌症之方法 |
| TWI833242B (zh) * | 2021-06-11 | 2024-02-21 | 大陸商廣東菲鵬製藥股份有限公司 | 抗pd-1人源化抗體或其抗原結合片段、編碼其的核酸、包含其的載體、細胞和藥物組合物及其用途 |
| US12448451B2 (en) | 2021-06-25 | 2025-10-21 | Chugai Seiyaku Kabushiki Kaisha | Anti-CTLA-4 antibody and use thereof |
| WO2023010098A2 (en) * | 2021-07-28 | 2023-02-02 | Elpiscience (Suzhou) Biopharma, Ltd. | Novel multi-specific molecules |
| CN113929785B (zh) * | 2021-09-10 | 2023-05-23 | 钦元再生医学(珠海)有限公司 | 一种可自分泌pd1-trem2双特异性抗体的嵌合抗原受体免疫细胞及其应用 |
| WO2024104409A1 (zh) * | 2022-11-16 | 2024-05-23 | 苏州盛迪亚生物医药有限公司 | 一种含抗rankl-ngf双特异性抗体的药物组合物 |
| WO2024126750A1 (en) * | 2022-12-15 | 2024-06-20 | F. Hoffmann-La Roche Ag | Methods for treating cancer |
| TW202434643A (zh) | 2023-01-09 | 2024-09-01 | 大陸商北京拓界生物醫藥科技有限公司 | ＴＧＦβ１結合分子、ＧＡＲＰ－ＴＧＦβ１結合分子及其醫藥用途 |
| TW202525857A (zh) * | 2023-09-11 | 2025-07-01 | 大陸商上海才致藥成生物科技有限公司 | 長效副甲狀腺激素受體促效劑融合蛋白及其應用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8242247B2 (en) * | 2007-12-21 | 2012-08-14 | Hoffmann-La Roche Inc. | Bivalent, bispecific antibodies |
| WO2011017294A1 (en) * | 2009-08-07 | 2011-02-10 | Schering Corporation | Human anti-rankl antibodies |
| MX2016008667A (es) * | 2013-12-30 | 2017-02-02 | Epimab Biotherapeutics Inc | Inmunoglobulina con fab en tandem y usos de esta. |
| CN104861067A (zh) * | 2014-01-10 | 2015-08-26 | 博笛生物科技有限公司 | 用于免疫疗法的化合物和组合物 |
| US20150307620A1 (en) * | 2014-04-16 | 2015-10-29 | University Of Connecticut | Linked immunotherapeutic agonists that costimulate multiple pathways |
| JO3663B1 (ar) * | 2014-08-19 | 2020-08-27 | Merck Sharp & Dohme | الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين |
| WO2016166139A1 (en) * | 2015-04-14 | 2016-10-20 | Eberhard Karls Universität Tübingen | Bispecific fusion proteins for enhancing immune responses of lymphocytes against tumor cells |
| MX2018009581A (es) * | 2016-02-06 | 2019-05-06 | Epimab Biotherapeutics Inc | Inmunoglobulina con fabs en tandem y sus usos. |
| DE202017007721U1 (de) * | 2016-05-20 | 2025-02-11 | Christoph Karl | Pharmazeutische Zusammensetzungen mit Anti-RANKL-Antikörpern, Kalzium und Vitamin D, geeignet zur Behandlung und/oder Prophylaxe von Erkrankungen des Knochenstoffwechsels und von therapiebedingten Nebenwirkungen wie Hypokalzämien |
| CA3034453A1 (en) * | 2016-08-25 | 2018-03-01 | AI Therapeutics, Inc. | Compositions comprising pikfyve inhibitors and methods related to inhibition of rank signaling |
-
2018
- 2018-06-05 JP JP2019567258A patent/JP2020522529A/ja active Pending
- 2018-06-05 US US16/619,891 patent/US20230042913A1/en not_active Abandoned
- 2018-06-05 CN CN201880050953.5A patent/CN111032085A/zh active Pending
- 2018-06-05 AU AU2018280340A patent/AU2018280340A1/en not_active Abandoned
- 2018-06-05 EP EP18813354.0A patent/EP3634484A4/en not_active Withdrawn
- 2018-06-05 CA CA3065836A patent/CA3065836A1/en active Pending
- 2018-06-05 WO PCT/AU2018/050557 patent/WO2018223182A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018223182A1 (en) | 2018-12-13 |
| JP2020522529A (ja) | 2020-07-30 |
| AU2018280340A1 (en) | 2019-12-19 |
| CN111032085A (zh) | 2020-04-17 |
| EP3634484A1 (en) | 2020-04-15 |
| US20230042913A1 (en) | 2023-02-09 |
| EP3634484A4 (en) | 2022-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230042913A1 (en) | A combination of, or a bispecific binding molecule to, an immune checkpoint molecule antagonist and a rank-l (nf-kb ligand) antagonist for cancer therapy or prophylaxis and uses thereof | |
| US11746157B2 (en) | PSMA binding agents and uses thereof | |
| TWI772275B (zh) | 特異性結合pd-1、tim-3或pd-1與tim-3之抗體及其用途 | |
| DK3097121T3 (en) | ANTIBODY MOLECULES AGAINST PD-1 AND APPLICATIONS THEREOF | |
| JP2021529556A (ja) | 抗腫瘍アンタゴニスト | |
| AU2018260505A1 (en) | Antibody conjugates comprising toll-like receptor agonist and combination therapies | |
| CA2987607A1 (en) | Tigit-binding agents and uses thereof | |
| US20190248901A1 (en) | Antibodies to mica and micb proteins | |
| US20220227876A1 (en) | Rank antagonists and uses thereof | |
| WO2017040660A1 (en) | Combination therapy for treatment of disease | |
| CN116390755A (zh) | 抗pd-1/cd40双特异性抗体及其用途 | |
| JP2024517986A (ja) | 抗－ＣＤ３００ｃ抗体を利用した併用療法 | |
| JP2024517985A (ja) | 抗－ＣＤ３００ｃモノクローナル抗体及びその癌の予防または治療用バイオマーカー | |
| EA046641B1 (ru) | Агенты, связывающиеся с psma, и виды их применения |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220929 |
|
| EEER | Examination request |
Effective date: 20220929 |
|
| EEER | Examination request |
Effective date: 20220929 |