CA2989144A1 - Treatment of cancer by combined blockade of the pd-1 and cxcr4 signaling pathways - Google Patents
Treatment of cancer by combined blockade of the pd-1 and cxcr4 signaling pathways Download PDFInfo
- Publication number
- CA2989144A1 CA2989144A1 CA2989144A CA2989144A CA2989144A1 CA 2989144 A1 CA2989144 A1 CA 2989144A1 CA 2989144 A CA2989144 A CA 2989144A CA 2989144 A CA2989144 A CA 2989144A CA 2989144 A1 CA2989144 A1 CA 2989144A1
- Authority
- CA
- Canada
- Prior art keywords
- antibody
- cxcr4
- antigen
- cancer
- binds specifically
- 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.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 251
- 201000011510 cancer Diseases 0.000 title claims abstract description 59
- 238000011282 treatment Methods 0.000 title claims description 91
- 230000019491 signal transduction Effects 0.000 title description 15
- 101100441540 Xenopus laevis cxcr4-a gene Proteins 0.000 title 1
- 101100441541 Xenopus laevis cxcr4-b gene Proteins 0.000 title 1
- 230000027455 binding Effects 0.000 claims abstract description 206
- 239000000427 antigen Substances 0.000 claims abstract description 169
- 102000036639 antigens Human genes 0.000 claims abstract description 167
- 108091007433 antigens Proteins 0.000 claims abstract description 167
- 238000000034 method Methods 0.000 claims abstract description 150
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 claims abstract description 124
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 claims abstract description 99
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 claims abstract description 98
- 102000008096 B7-H1 Antigen Human genes 0.000 claims abstract description 72
- 108010074708 B7-H1 Antigen Proteins 0.000 claims abstract description 72
- 102000005962 receptors Human genes 0.000 claims abstract description 13
- 108020003175 receptors Proteins 0.000 claims abstract description 13
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 claims abstract description 7
- 108050006947 CXC Chemokine Proteins 0.000 claims abstract description 6
- 102000019388 CXC chemokine Human genes 0.000 claims abstract description 6
- 229950010095 ulocuplumab Drugs 0.000 claims description 120
- 229960003301 nivolumab Drugs 0.000 claims description 107
- 241000282414 Homo sapiens Species 0.000 claims description 87
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 83
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 77
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 54
- 201000002528 pancreatic cancer Diseases 0.000 claims description 54
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 51
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 51
- 230000003442 weekly effect Effects 0.000 claims description 48
- 230000037396 body weight Effects 0.000 claims description 31
- 230000011664 signaling Effects 0.000 claims description 25
- 230000003993 interaction Effects 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 22
- 230000001988 toxicity Effects 0.000 claims description 22
- 231100000419 toxicity Toxicity 0.000 claims description 22
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims description 20
- 102000048362 human PDCD1 Human genes 0.000 claims description 19
- 239000012636 effector Substances 0.000 claims description 18
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 17
- 230000008901 benefit Effects 0.000 claims description 16
- 230000006870 function Effects 0.000 claims description 16
- 230000002411 adverse Effects 0.000 claims description 15
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 13
- 230000004540 complement-dependent cytotoxicity Effects 0.000 claims description 12
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 12
- 229960002621 pembrolizumab Drugs 0.000 claims description 12
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 12
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 11
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims description 11
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 11
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 11
- 102000048776 human CD274 Human genes 0.000 claims description 11
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- 102000053523 human CXCR4 Human genes 0.000 claims description 10
- 206010061818 Disease progression Diseases 0.000 claims description 9
- 230000005750 disease progression Effects 0.000 claims description 9
- 201000007270 liver cancer Diseases 0.000 claims description 9
- 208000014018 liver neoplasm Diseases 0.000 claims description 9
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 8
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 8
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 7
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 7
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 7
- 238000001990 intravenous administration Methods 0.000 claims description 7
- 201000001441 melanoma Diseases 0.000 claims description 6
- 208000017604 Hodgkin disease Diseases 0.000 claims description 5
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 5
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 5
- 229960003852 atezolizumab Drugs 0.000 claims description 5
- 229950009791 durvalumab Drugs 0.000 claims description 5
- 230000001394 metastastic effect Effects 0.000 claims description 5
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 229950002916 avelumab Drugs 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- 201000008443 lung non-squamous non-small cell carcinoma Diseases 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006143 Brain stem glioma Diseases 0.000 claims description 2
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims description 2
- 206010007953 Central nervous system lymphoma Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
- 208000021309 Germ cell tumor Diseases 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 208000000821 Parathyroid Neoplasms Diseases 0.000 claims description 2
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 2
- 201000005746 Pituitary adenoma Diseases 0.000 claims description 2
- 206010061538 Pituitary tumour benign Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000004346 Smoldering Multiple Myeloma Diseases 0.000 claims description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 2
- 206010057644 Testis cancer Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims description 2
- 206010046458 Urethral neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 201000003761 Vaginal carcinoma Diseases 0.000 claims description 2
- 241000700605 Viruses Species 0.000 claims description 2
- 208000024447 adrenal gland neoplasm Diseases 0.000 claims description 2
- 208000025997 central nervous system neoplasm Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 208000019065 cervical carcinoma Diseases 0.000 claims description 2
- 210000000750 endocrine system Anatomy 0.000 claims description 2
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 2
- 201000001343 fallopian tube carcinoma Diseases 0.000 claims description 2
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 claims description 2
- 210000002990 parathyroid gland Anatomy 0.000 claims description 2
- 208000021310 pituitary gland adenoma Diseases 0.000 claims description 2
- 208000016800 primary central nervous system lymphoma Diseases 0.000 claims description 2
- 230000000306 recurrent effect Effects 0.000 claims description 2
- 201000007444 renal pelvis carcinoma Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 201000009295 smoldering myeloma Diseases 0.000 claims description 2
- 208000010721 smoldering plasma cell myeloma Diseases 0.000 claims description 2
- 208000017572 squamous cell neoplasm Diseases 0.000 claims description 2
- 201000003120 testicular cancer Diseases 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 230000005747 tumor angiogenesis Effects 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 208000013013 vulvar carcinoma Diseases 0.000 claims description 2
- 206010066476 Haematological malignancy Diseases 0.000 claims 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 claims 2
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 claims 2
- 210000004027 cell Anatomy 0.000 description 76
- 238000011156 evaluation Methods 0.000 description 55
- 238000004458 analytical method Methods 0.000 description 46
- 125000003275 alpha amino acid group Chemical group 0.000 description 40
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 40
- 230000004044 response Effects 0.000 description 40
- 239000003814 drug Substances 0.000 description 39
- 241000699666 Mus <mouse, genus> Species 0.000 description 37
- 230000000694 effects Effects 0.000 description 37
- 238000001802 infusion Methods 0.000 description 37
- 241000699670 Mus sp. Species 0.000 description 36
- 201000010099 disease Diseases 0.000 description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 34
- 210000004881 tumor cell Anatomy 0.000 description 34
- 210000003289 regulatory T cell Anatomy 0.000 description 31
- 210000001744 T-lymphocyte Anatomy 0.000 description 28
- 239000003795 chemical substances by application Substances 0.000 description 27
- 238000013461 design Methods 0.000 description 27
- 229940079593 drug Drugs 0.000 description 27
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 description 26
- 238000002560 therapeutic procedure Methods 0.000 description 25
- 230000000259 anti-tumor effect Effects 0.000 description 24
- 238000009097 single-agent therapy Methods 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 23
- 230000004614 tumor growth Effects 0.000 description 23
- 230000000052 comparative effect Effects 0.000 description 22
- 230000005764 inhibitory process Effects 0.000 description 22
- 239000012634 fragment Substances 0.000 description 21
- 230000002401 inhibitory effect Effects 0.000 description 21
- 230000004083 survival effect Effects 0.000 description 19
- 238000002512 chemotherapy Methods 0.000 description 15
- 238000002648 combination therapy Methods 0.000 description 15
- 230000006907 apoptotic process Effects 0.000 description 14
- 230000001506 immunosuppresive effect Effects 0.000 description 13
- 229960005277 gemcitabine Drugs 0.000 description 12
- 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 description 12
- 230000035772 mutation Effects 0.000 description 12
- 230000037361 pathway Effects 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 238000000684 flow cytometry Methods 0.000 description 11
- 239000003446 ligand Substances 0.000 description 11
- 150000001413 amino acids Chemical class 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 230000034994 death Effects 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- 210000004602 germ cell Anatomy 0.000 description 10
- 230000005847 immunogenicity Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 108060003951 Immunoglobulin Proteins 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 102000043525 human CXCL12 Human genes 0.000 description 9
- 102000018358 immunoglobulin Human genes 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 8
- 239000000090 biomarker Substances 0.000 description 8
- 230000000903 blocking effect Effects 0.000 description 8
- 230000003111 delayed effect Effects 0.000 description 8
- 210000002865 immune cell Anatomy 0.000 description 8
- 229960003444 immunosuppressant agent Drugs 0.000 description 8
- 230000001861 immunosuppressant effect Effects 0.000 description 8
- 239000003018 immunosuppressive agent Substances 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 238000010172 mouse model Methods 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 8
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 7
- 206010025323 Lymphomas Diseases 0.000 description 7
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 7
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 7
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 7
- 238000001574 biopsy Methods 0.000 description 7
- 230000001364 causal effect Effects 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 201000000050 myeloid neoplasm Diseases 0.000 description 7
- 208000037821 progressive disease Diseases 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 6
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 6
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 6
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 102100023832 Prolyl endopeptidase FAP Human genes 0.000 description 6
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 6
- 230000022534 cell killing Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 230000000779 depleting effect Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 5
- 230000009977 dual effect Effects 0.000 description 5
- 230000002708 enhancing effect Effects 0.000 description 5
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 5
- PJZDLZXMGBOJRF-CXOZILEQSA-L folfirinox Chemical compound [Pt+4].[O-]C(=O)C([O-])=O.[NH-][C@H]1CCCC[C@@H]1[NH-].FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 PJZDLZXMGBOJRF-CXOZILEQSA-L 0.000 description 5
- 201000003444 follicular lymphoma Diseases 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 230000003902 lesion Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 230000007115 recruitment Effects 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 238000013517 stratification Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- WAVYAFBQOXCGSZ-UHFFFAOYSA-N 2-fluoropyrimidine Chemical compound FC1=NC=CC=N1 WAVYAFBQOXCGSZ-UHFFFAOYSA-N 0.000 description 4
- 108010061299 CXCR4 Receptors Proteins 0.000 description 4
- 102000012000 CXCR4 Receptors Human genes 0.000 description 4
- 238000012286 ELISA Assay Methods 0.000 description 4
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000006052 T cell proliferation Effects 0.000 description 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 4
- 238000011319 anticancer therapy Methods 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000002489 hematologic effect Effects 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 229960005386 ipilimumab Drugs 0.000 description 4
- 238000011551 log transformation method Methods 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000010534 mechanism of action Effects 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 210000002536 stromal cell Anatomy 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 3
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 208000002460 Enteropathy-Associated T-Cell Lymphoma Diseases 0.000 description 3
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010061309 Neoplasm progression Diseases 0.000 description 3
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000003698 anagen phase Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 230000003185 calcium uptake Effects 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 3
- 229960005420 etoposide Drugs 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 230000001024 immunotherapeutic effect Effects 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 201000005962 mycosis fungoides Diseases 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 229960002169 plerixafor Drugs 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 238000010188 recombinant method Methods 0.000 description 3
- 231100000279 safety data Toxicity 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 230000009044 synergistic interaction Effects 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 229950007217 tremelimumab Drugs 0.000 description 3
- 230000005751 tumor progression Effects 0.000 description 3
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 229960003862 vemurafenib Drugs 0.000 description 3
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 description 3
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 2
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 2
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 2
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 description 2
- 108010074051 C-Reactive Protein Proteins 0.000 description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 2
- 102100032752 C-reactive protein Human genes 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 206010072268 Drug-induced liver injury Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 2
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 2
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 2
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 2
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 101000611935 Mus musculus Programmed cell death protein 1 Proteins 0.000 description 2
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 2
- 241000237988 Patellidae Species 0.000 description 2
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 2
- 206010070308 Refractory cancer Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 206010042971 T-cell lymphoma Diseases 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 210000005006 adaptive immune system Anatomy 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000003466 anti-cipated effect Effects 0.000 description 2
- 230000006023 anti-tumor response Effects 0.000 description 2
- 230000009464 antigen specific memory response Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 238000002619 cancer immunotherapy Methods 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 201000010897 colon adenocarcinoma Diseases 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 230000009850 completed effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 229940121384 cxc chemokine receptor type 4 (cxcr4) antagonist Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000009266 disease activity Effects 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- -1 e.g. Proteins 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 2
- 235000008191 folinic acid Nutrition 0.000 description 2
- 239000011672 folinic acid Substances 0.000 description 2
- 238000011223 gene expression profiling Methods 0.000 description 2
- 235000015220 hamburgers Nutrition 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 108060003552 hemocyanin Proteins 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 230000005746 immune checkpoint blockade Effects 0.000 description 2
- 230000008629 immune suppression Effects 0.000 description 2
- 230000037451 immune surveillance Effects 0.000 description 2
- 230000003259 immunoinhibitory effect Effects 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 229960001691 leucovorin Drugs 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 210000004897 n-terminal region Anatomy 0.000 description 2
- 210000004967 non-hematopoietic stem cell Anatomy 0.000 description 2
- 229940127084 other anti-cancer agent Drugs 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 210000004197 pelvis Anatomy 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000011176 pooling Methods 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229960003787 sorafenib Drugs 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229940073184 sunitinib 37.5 mg Drugs 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 230000004565 tumor cell growth Effects 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 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 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
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- 206010001413 Adult T-cell lymphoma/leukaemia Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002412 Angiocentric lymphomas Diseases 0.000 description 1
- 102100022716 Atypical chemokine receptor 3 Human genes 0.000 description 1
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 101710082513 C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 101150066398 CXCR4 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 201000005488 Capillary Leak Syndrome Diseases 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 1
- 238000000959 Cochran–Mantel–Haenszel (CMH) test Methods 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 208000019872 Drug Eruptions Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010072063 Exposure to lead Diseases 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 208000002291 Histiocytic Sarcoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000678890 Homo sapiens Atypical chemokine receptor 3 Proteins 0.000 description 1
- 101100166600 Homo sapiens CD28 gene Proteins 0.000 description 1
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 1
- 101001042104 Homo sapiens Inducible T-cell costimulator Proteins 0.000 description 1
- 101001027081 Homo sapiens Killer cell immunoglobulin-like receptor 2DL1 Proteins 0.000 description 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102100037363 Killer cell immunoglobulin-like receptor 2DL1 Human genes 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100497626 Mus musculus Cxcr4 gene Proteins 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 101100109397 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) arg-8 gene Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 108090000526 Papain Proteins 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
- 206010034623 Peripheral T-cell lymphoma unspecified Diseases 0.000 description 1
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 206010036524 Precursor B-lymphoblastic lymphomas Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000032758 Precursor T-lymphoblastic lymphoma/leukaemia Diseases 0.000 description 1
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010038111 Recurrent cancer Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- 206010042434 Sudden death Diseases 0.000 description 1
- 208000031932 Systemic capillary leak syndrome Diseases 0.000 description 1
- 230000022924 T cell antigen processing and presentation Effects 0.000 description 1
- 230000006043 T cell recruitment Effects 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
- 201000011648 T-cell childhood lymphoblastic lymphoma Diseases 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 208000020982 T-lymphoblastic lymphoma Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 231100000230 acceptable toxicity Toxicity 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 206010002449 angioimmunoblastic T-cell lymphoma Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 231100001015 blood dyscrasias Toxicity 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 230000005887 cellular phagocytosis Effects 0.000 description 1
- 239000002576 chemokine receptor CXCR4 antagonist Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 206010061811 demyelinating polyneuropathy Diseases 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 208000037902 enteropathy Diseases 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000004076 epigenetic alteration Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 230000006028 immune-suppresssive effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000013394 immunophenotyping Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000009863 impact test Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 208000015266 indolent plasma cell myeloma Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 201000001268 lymphoproliferative syndrome Diseases 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 1
- 208000021937 marginal zone lymphoma Diseases 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 229940074923 mozobil Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 238000011518 platinum-based chemotherapy Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 201000006037 primary mediastinal B-cell lymphoma Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011470 radical surgery Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000000985 reactive dye Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 102200055464 rs113488022 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000011519 second-line treatment Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000010206 sensitivity analysis Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- 239000000107 tumor biomarker Substances 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 238000013414 tumor xenograft model Methods 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 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
- C07K16/28—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- 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
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate 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
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- 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
- C07K2317/72—Increased effector function due to an Fc-modification
-
- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- 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]
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562174931P | 2015-06-12 | 2015-06-12 | |
| US62/174,931 | 2015-06-12 | ||
| PCT/US2016/037207 WO2016201425A1 (en) | 2015-06-12 | 2016-06-13 | Treatment of cancer by combined blockade of the pd-1 and cxcr4 signaling pathways |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2989144A1 true CA2989144A1 (en) | 2016-12-15 |
Family
ID=56194616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2989144A Abandoned CA2989144A1 (en) | 2015-06-12 | 2016-06-13 | Treatment of cancer by combined blockade of the pd-1 and cxcr4 signaling pathways |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20180179282A1 (enExample) |
| EP (1) | EP3307778A1 (enExample) |
| JP (1) | JP2018516969A (enExample) |
| CN (1) | CN108026173A (enExample) |
| BR (1) | BR112017026189A2 (enExample) |
| CA (1) | CA2989144A1 (enExample) |
| EA (1) | EA201792522A1 (enExample) |
| MX (1) | MX2017015811A (enExample) |
| WO (1) | WO2016201425A1 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006265108C1 (en) * | 2005-07-01 | 2013-01-17 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death ligand 1 (PD-L1) |
| CA3213528A1 (en) * | 2012-05-15 | 2013-11-21 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
| US10478494B2 (en) | 2015-04-03 | 2019-11-19 | Astex Therapeutics Ltd | FGFR/PD-1 combination therapy for the treatment of cancer |
| JP6958820B2 (ja) | 2015-12-14 | 2021-11-02 | エックス４ ファーマシューティカルズ， インコーポレイテッド | がんを処置する方法 |
| CA3008272A1 (en) | 2015-12-14 | 2017-06-22 | X4 Pharmaceuticals, Inc. | Methods for treating cancer |
| SI3393468T1 (sl) | 2015-12-22 | 2023-01-31 | X4 Pharmaceuticals, Inc. | Postopki za zdravljenje bolezni imunske pomanjkljivosti |
| CN108883132A (zh) * | 2016-01-22 | 2018-11-23 | X4 制药有限公司 | 用于治疗癌症的方法 |
| WO2017177230A1 (en) | 2016-04-08 | 2017-10-12 | X4 Pharmaceuticals, Inc. | Methods for treating cancer |
| CN109641838A (zh) | 2016-06-21 | 2019-04-16 | X4 制药有限公司 | Cxcr4抑制剂及其用途 |
| JP7054529B2 (ja) | 2016-06-21 | 2022-04-14 | エックス４ ファーマシューティカルズ， インコーポレイテッド | Ｃｘｃｒ４阻害剤およびその使用 |
| EP3471726A4 (en) | 2016-06-21 | 2019-10-09 | X4 Pharmaceuticals, Inc. | CXCR4 INHIBITORS AND USES THEREOF |
| US20190307821A1 (en) * | 2016-11-29 | 2019-10-10 | Health Research, Inc. | Methods and compositions for cancer therapy |
| WO2018175676A1 (en) | 2017-03-23 | 2018-09-27 | The General Hospital Corporation | Cxcr4/cxcr7 blockade and treatment of human papilloma virus-associated disease |
| US20190233524A1 (en) * | 2017-09-18 | 2019-08-01 | Tcm Biotech International Corp. | Therapeutic combination and method for treating cancer |
| CN109517039B (zh) * | 2017-09-20 | 2021-03-19 | 尚华医药科技(江西)有限公司 | 一种肽类化合物、其应用及含其的组合物 |
| CA3080821A1 (en) * | 2017-11-07 | 2019-05-16 | X4 Pharmaceuticals, Inc. | Cancer biomarkers and methods of use thereof |
| ES2973728T3 (es) * | 2018-03-13 | 2024-06-24 | Fundacion Para La Investigacion Biomedica Del Hospital Univ La Paz | Anticuerpo anti-CXCR4 combinado con linfocitos citolíticos naturales activados y expandidos para inmunoterapia contra el cáncer |
| US10548889B1 (en) | 2018-08-31 | 2020-02-04 | X4 Pharmaceuticals, Inc. | Compositions of CXCR4 inhibitors and methods of preparation and use |
| CA3115802A1 (en) | 2018-10-17 | 2020-04-23 | Biolinerx Ltd. | Treatment of metastatic pancreatic adenocarcinoma |
| WO2020135415A1 (zh) * | 2018-12-24 | 2020-07-02 | 正大天晴药业集团股份有限公司 | 抗pd-l1单克隆抗体治疗癌症的用途 |
| US12497439B2 (en) | 2019-01-07 | 2025-12-16 | Thomas Jefferson University | Multi-functional fusion proteins and uses thereof |
| JP7547360B2 (ja) * | 2019-03-22 | 2024-09-09 | スミトモ ファーマ オンコロジー， インコーポレイテッド | Ｐｋｍ２モジュレーターを含む組成物およびそれを使用する処置の方法 |
| JP2023517956A (ja) | 2020-03-10 | 2023-04-27 | エックス４ ファーマシューティカルズ， インコーポレイテッド | 好中球減少症を処置する方法 |
| CA3247048A1 (en) | 2022-04-13 | 2023-10-19 | Genentech, Inc. | PHARMACEUTICAL COMPOSITIONS OF MOSUNETUZUMAB AND METHODS OF USE |
| KR20250004768A (ko) | 2022-04-13 | 2025-01-08 | 제넨테크, 인크. | 치료 단백질의 약학적 조성물 및 사용 방법 |
| AR129203A1 (es) * | 2022-05-04 | 2024-07-31 | Janux Therapeutics Inc | Anticuerpos multiespecíficos activados por tumores para dirigirse a cd28 y pd-l1, y métodos para usarlos |
| CN115487146B (zh) * | 2022-10-28 | 2023-07-18 | 宁夏医科大学 | 一种阻断cxcr4/pd-l1双信号的三药共递送纳米体系及其制备方法和应用 |
| WO2024120084A1 (zh) * | 2022-12-07 | 2024-06-13 | 宜明昂科生物医药技术（上海）股份有限公司 | 使用cd24抗体和pd-1-pd-l1通路阻断抗体的癌症联合疗法 |
| CN120813375A (zh) * | 2023-01-30 | 2025-10-17 | 凯玛布有限公司 | 抗体 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6682736B1 (en) | 1998-12-23 | 2004-01-27 | Abgenix, Inc. | Human monoclonal antibodies to CTLA-4 |
| ES2367430T3 (es) | 2002-12-23 | 2011-11-03 | Wyeth Llc | Anticuerpos contra pd-1 y sus usos. |
| AU2006244885B2 (en) | 2005-05-09 | 2011-03-31 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| AU2006265108C1 (en) | 2005-07-01 | 2013-01-17 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death ligand 1 (PD-L1) |
| JP5244785B2 (ja) | 2006-08-11 | 2013-07-24 | 小野薬品工業株式会社 | ストローマ由来因子−１（ｓｄｆ−１）に対するモノクローナル抗体 |
| EP2066351B1 (en) | 2006-10-02 | 2015-09-09 | E. R. Squibb & Sons, L.L.C. | Human antibodies that bind cxcr4 and uses thereof |
| FR2915102B1 (fr) | 2007-04-23 | 2014-05-16 | Pf Medicament | Utilisation d'un anticorps anti-cxcr4 pour le traitement du cancer |
| CA2691357C (en) | 2007-06-18 | 2014-09-23 | N.V. Organon | Antibodies to human programmed death receptor pd-1 |
| EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
| US7892546B2 (en) | 2008-05-14 | 2011-02-22 | Eli Lilly And Company | Anti-CXCR4 antibodies |
| JP2011520885A (ja) | 2008-05-14 | 2011-07-21 | イーライ リリー アンド カンパニー | 抗ｃｘｃｒ４抗体 |
| MX2011002250A (es) * | 2008-08-25 | 2011-08-17 | Amplimmune Inc | Antagonistas de muerte celular programada-1 y métodos de uso de los mismos. |
| EP2172485A1 (en) | 2008-10-01 | 2010-04-07 | Pierre Fabre Medicament | Novel anti CXCR4 antibodies and their use for the treatment of cancer |
| PT2376535T (pt) | 2008-12-09 | 2017-06-23 | Hoffmann La Roche | Anticorpos anti-pd-l1 e a sua utilização para a melhoria do funcionamento das células t |
| WO2011066389A1 (en) | 2009-11-24 | 2011-06-03 | Medimmmune, Limited | Targeted binding agents against b7-h1 |
| RS57324B1 (sr) | 2011-04-20 | 2018-08-31 | Medimmune Llc | Antitela i drugi molekuli koji vezuju b7-h1 i pd-1 |
| CA2842169A1 (en) | 2011-07-20 | 2013-01-24 | Medimmune Limited | Anti-cxcr4 antibodies and methods of use |
| ES2705001T3 (es) | 2011-11-09 | 2019-03-21 | Bristol Myers Squibb Co | Tratamiento de neoplasias hematológicas con un anticuerpo anti-CXCR4 |
| CA2856895C (en) | 2011-11-28 | 2021-10-26 | Merck Patent Gmbh | Anti-pd-l1 antibodies and uses thereof |
| CA3213528A1 (en) | 2012-05-15 | 2013-11-21 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
| EP2854843A4 (en) | 2012-05-31 | 2016-06-01 | Sorrento Therapeutics Inc | ANTIGEN-BINDING PROTEINS FOR BINDING PD-L1 |
| PL2925350T3 (pl) | 2012-12-03 | 2019-07-31 | Bristol-Myers Squibb Company | Zwiększenie aktywności przeciwnowotworowej immunomodulacyjnych białek fuzyjnych fc |
| EP4050033A1 (en) | 2013-08-02 | 2022-08-31 | Pfizer Inc. | Anti-cxcr4 antibodies and antibody-drug conjugates |
| EP3030322A2 (en) * | 2013-08-05 | 2016-06-15 | Cambridge Enterprise Limited | Inhibition of cxcr4 signaling in cancer immunotherapy |
-
2016
- 2016-06-13 BR BR112017026189A patent/BR112017026189A2/pt not_active IP Right Cessation
- 2016-06-13 EP EP16731754.4A patent/EP3307778A1/en not_active Withdrawn
- 2016-06-13 EA EA201792522A patent/EA201792522A1/ru unknown
- 2016-06-13 US US15/735,055 patent/US20180179282A1/en not_active Abandoned
- 2016-06-13 WO PCT/US2016/037207 patent/WO2016201425A1/en not_active Ceased
- 2016-06-13 CA CA2989144A patent/CA2989144A1/en not_active Abandoned
- 2016-06-13 CN CN201680047043.2A patent/CN108026173A/zh active Pending
- 2016-06-13 JP JP2017564421A patent/JP2018516969A/ja not_active Withdrawn
- 2016-06-13 MX MX2017015811A patent/MX2017015811A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR112017026189A2 (pt) | 2018-08-14 |
| EP3307778A1 (en) | 2018-04-18 |
| WO2016201425A1 (en) | 2016-12-15 |
| EA201792522A1 (ru) | 2018-05-31 |
| JP2018516969A (ja) | 2018-06-28 |
| WO2016201425A9 (en) | 2017-01-19 |
| US20180179282A1 (en) | 2018-06-28 |
| CN108026173A (zh) | 2018-05-11 |
| MX2017015811A (es) | 2018-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20180179282A1 (en) | Treatment of cancer by combined blockade of the pd-1 and cxcr4 signaling pathways | |
| US20250011466A1 (en) | Treatment of lung cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent | |
| RU2766890C2 (ru) | Комбинированные способы лечения антагонистами pd-l1 | |
| US10023649B2 (en) | Method of treating cancer with a combination of an anti-CCR4 antibody and a 4-1BB agonist | |
| CN106573977B (zh) | 针对ceacam1的人源化抗体 | |
| JP2024020202A (ja) | リンパ腫処置における抗ｃｄ３０抗体と組み合わせた抗ｐｄ－１抗体の使用 | |
| CN111699005A (zh) | 使用抗cd47抗体和抗cd20抗体的抗癌方案 | |
| CN104470949A (zh) | 通过破坏pd-1/pd-l1信号传输的免疫治疗 | |
| US20210054063A1 (en) | Combination therapy with anti-il-8 antibodies and anti-pd-1 antibodies for treating cancer | |
| WO2017165125A1 (en) | Use of a pd-1 antagonist and an anti-ccr2 antibody in the treatment of cancer | |
| CA3224890A1 (en) | Lag-3 antagonist therapy for hematological cancer | |
| US20240092934A1 (en) | Assessment of ceacam1 expression on tumor infiltrating lymphocytes | |
| HK1233518A1 (en) | Combination of an anti-ccr4 antibody and a 4-1bb agonist for treating cancer | |
| HK1248530B (en) | Pd-l1 antagonist combination treatments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220301 |