CN113621073A - 一种新型嵌合受体组合物、重组载体、细胞及其应用 - Google Patents
一种新型嵌合受体组合物、重组载体、细胞及其应用 Download PDFInfo
- Publication number
- CN113621073A CN113621073A CN202110793058.6A CN202110793058A CN113621073A CN 113621073 A CN113621073 A CN 113621073A CN 202110793058 A CN202110793058 A CN 202110793058A CN 113621073 A CN113621073 A CN 113621073A
- Authority
- CN
- China
- Prior art keywords
- leu
- ser
- gly
- ala
- pro
- 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.)
- Withdrawn
Links
- 108700010039 chimeric receptor Proteins 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims abstract description 43
- 239000013598 vector Substances 0.000 title claims abstract description 21
- 210000004027 cell Anatomy 0.000 claims abstract description 92
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims abstract description 39
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims abstract description 39
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 28
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 20
- 239000000427 antigen Substances 0.000 claims abstract description 19
- 108091007433 antigens Proteins 0.000 claims abstract description 19
- 102000036639 antigens Human genes 0.000 claims abstract description 19
- 230000003834 intracellular effect Effects 0.000 claims abstract description 14
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 claims abstract description 13
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 claims abstract description 13
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 claims abstract description 10
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 claims abstract description 10
- 239000012634 fragment Substances 0.000 claims abstract description 7
- -1 ICOS Proteins 0.000 claims description 28
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 22
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 12
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 12
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 12
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 12
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 12
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 12
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 12
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims description 12
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 12
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 12
- 150000007523 nucleic acids Chemical group 0.000 claims description 12
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 11
- 102100025390 Integrin beta-2 Human genes 0.000 claims description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 10
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 10
- 101150013553 CD40 gene Proteins 0.000 claims description 9
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 102100027207 CD27 antigen Human genes 0.000 claims description 6
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 6
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims description 6
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 claims description 6
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims description 6
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 6
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 claims description 6
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 6
- 102100034256 Mucin-1 Human genes 0.000 claims description 6
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 4
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 4
- 108010075254 C-Peptide Proteins 0.000 claims description 4
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 4
- 210000000822 natural killer cell Anatomy 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims description 3
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 3
- 102100023635 Alpha-fetoprotein Human genes 0.000 claims description 3
- 101001005269 Arabidopsis thaliana Ceramide synthase 1 LOH3 Proteins 0.000 claims description 3
- 101001005312 Arabidopsis thaliana Ceramide synthase LOH1 Proteins 0.000 claims description 3
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 3
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 3
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 3
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 3
- 102100026094 C-type lectin domain family 12 member A Human genes 0.000 claims description 3
- 101710188619 C-type lectin domain family 12 member A Proteins 0.000 claims description 3
- 102100024209 CD177 antigen Human genes 0.000 claims description 3
- 102100025221 CD70 antigen Human genes 0.000 claims description 3
- 102100028801 Calsyntenin-1 Human genes 0.000 claims description 3
- 102100038449 Claudin-6 Human genes 0.000 claims description 3
- 108090000229 Claudin-6 Proteins 0.000 claims description 3
- 102100036466 Delta-like protein 3 Human genes 0.000 claims description 3
- 101710088083 Glomulin Proteins 0.000 claims description 3
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 3
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 3
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 3
- 101000980845 Homo sapiens CD177 antigen Proteins 0.000 claims description 3
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 claims description 3
- 101000928513 Homo sapiens Delta-like protein 3 Proteins 0.000 claims description 3
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 3
- 101001015037 Homo sapiens Integrin beta-7 Proteins 0.000 claims description 3
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 claims description 3
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 3
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 3
- 101000620359 Homo sapiens Melanocyte protein PMEL Proteins 0.000 claims description 3
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 claims description 3
- 101001051490 Homo sapiens Neural cell adhesion molecule L1 Proteins 0.000 claims description 3
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 claims description 3
- 101000831616 Homo sapiens Protachykinin-1 Proteins 0.000 claims description 3
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 claims description 3
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 claims description 3
- 101000662909 Homo sapiens T cell receptor beta constant 1 Proteins 0.000 claims description 3
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 claims description 3
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims description 3
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 claims description 3
- 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 claims description 3
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 3
- 101000807561 Homo sapiens Tyrosine-protein kinase receptor UFO Proteins 0.000 claims description 3
- 101710123134 Ice-binding protein Proteins 0.000 claims description 3
- 101710082837 Ice-structuring protein Proteins 0.000 claims description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 3
- 102100033016 Integrin beta-7 Human genes 0.000 claims description 3
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 claims description 3
- 101150113776 LMP1 gene Proteins 0.000 claims description 3
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 3
- 102100022430 Melanocyte protein PMEL Human genes 0.000 claims description 3
- 102000003729 Neprilysin Human genes 0.000 claims description 3
- 108090000028 Neprilysin Proteins 0.000 claims description 3
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims description 3
- 102100024964 Neural cell adhesion molecule L1 Human genes 0.000 claims description 3
- 102100040120 Prominin-1 Human genes 0.000 claims description 3
- 102100024304 Protachykinin-1 Human genes 0.000 claims description 3
- 101000668858 Spinacia oleracea 30S ribosomal protein S1, chloroplastic Proteins 0.000 claims description 3
- 101000898746 Streptomyces clavuligerus Clavaminate synthase 1 Proteins 0.000 claims description 3
- 102100035721 Syndecan-1 Human genes 0.000 claims description 3
- 102100037272 T cell receptor beta constant 1 Human genes 0.000 claims description 3
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims description 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 3
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 claims description 3
- 108020000411 Toll-like receptor Proteins 0.000 claims description 3
- 102000002689 Toll-like receptor Human genes 0.000 claims description 3
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 3
- 101710107540 Type-2 ice-structuring protein Proteins 0.000 claims description 3
- 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 claims description 3
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 claims description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 210000002203 alpha-beta t lymphocyte Anatomy 0.000 claims description 3
- 239000003124 biologic agent Substances 0.000 claims description 3
- 238000005520 cutting process Methods 0.000 claims description 3
- 229940127276 delta-like ligand 3 Drugs 0.000 claims description 3
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 claims description 3
- 210000002540 macrophage Anatomy 0.000 claims description 3
- 210000000581 natural killer T-cell Anatomy 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 claims 3
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000009977 dual effect Effects 0.000 abstract description 22
- 230000002147 killing effect Effects 0.000 abstract description 14
- 238000001228 spectrum Methods 0.000 abstract description 4
- 210000004881 tumor cell Anatomy 0.000 abstract description 3
- 108010026333 seryl-proline Proteins 0.000 description 15
- 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 13
- RJIVPOXLQFJRTG-LURJTMIESA-N Gly-Arg-Gly Chemical compound OC(=O)CNC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N RJIVPOXLQFJRTG-LURJTMIESA-N 0.000 description 11
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 10
- 108010079364 N-glycylalanine Proteins 0.000 description 9
- 108010060199 cysteinylproline Proteins 0.000 description 9
- JGLWFWXGOINXEA-YDHLFZDLSA-N Asp-Val-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 JGLWFWXGOINXEA-YDHLFZDLSA-N 0.000 description 8
- COWHUQXTSYTKQC-RWRJDSDZSA-N Ile-Thr-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N COWHUQXTSYTKQC-RWRJDSDZSA-N 0.000 description 8
- 108020003285 Isocitrate lyase Proteins 0.000 description 8
- SBANPBVRHYIMRR-UHFFFAOYSA-N Leu-Ser-Pro Natural products CC(C)CC(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O SBANPBVRHYIMRR-UHFFFAOYSA-N 0.000 description 8
- WTZUSCUIVPVCRH-SRVKXCTJSA-N Lys-Gln-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WTZUSCUIVPVCRH-SRVKXCTJSA-N 0.000 description 8
- 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 description 8
- ONNSECRQFSTMCC-XKBZYTNZSA-N Thr-Glu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O ONNSECRQFSTMCC-XKBZYTNZSA-N 0.000 description 8
- 108010016616 cysteinylglycine Proteins 0.000 description 8
- 239000010445 mica Substances 0.000 description 8
- 229910052618 mica group Inorganic materials 0.000 description 8
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 7
- GLWFAWNYGWBMOC-SRVKXCTJSA-N Asn-Leu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GLWFAWNYGWBMOC-SRVKXCTJSA-N 0.000 description 7
- JESJDAAGXULQOP-CIUDSAMLSA-N Gln-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)CN=C(N)N JESJDAAGXULQOP-CIUDSAMLSA-N 0.000 description 7
- QSQXZZCGPXQBPP-BQBZGAKWSA-N Gly-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)CN)C(=O)N[C@@H](CS)C(=O)O QSQXZZCGPXQBPP-BQBZGAKWSA-N 0.000 description 7
- LXKNSJLSGPNHSK-KKUMJFAQSA-N Leu-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N LXKNSJLSGPNHSK-KKUMJFAQSA-N 0.000 description 7
- KAJLHCWRWDSROH-BZSNNMDCSA-N Phe-Phe-Asp Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(O)=O)C(O)=O)C1=CC=CC=C1 KAJLHCWRWDSROH-BZSNNMDCSA-N 0.000 description 7
- WVXQQUWOKUZIEG-VEVYYDQMSA-N Pro-Thr-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O WVXQQUWOKUZIEG-VEVYYDQMSA-N 0.000 description 7
- BGOWRLSWJCVYAQ-CIUDSAMLSA-N Ser-Asp-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O BGOWRLSWJCVYAQ-CIUDSAMLSA-N 0.000 description 7
- CDVFZMOFNJPUDD-ACZMJKKPSA-N Ser-Gln-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CDVFZMOFNJPUDD-ACZMJKKPSA-N 0.000 description 7
- GMXIJHCBTZDAPD-QPHKQPEJSA-N Thr-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N GMXIJHCBTZDAPD-QPHKQPEJSA-N 0.000 description 7
- JJNXZIPLIXIGBX-HJPIBITLSA-N Tyr-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N JJNXZIPLIXIGBX-HJPIBITLSA-N 0.000 description 7
- YTNGABPUXFEOGU-SRVKXCTJSA-N Val-Pro-Arg Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O YTNGABPUXFEOGU-SRVKXCTJSA-N 0.000 description 7
- 108010038633 aspartylglutamate Proteins 0.000 description 7
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- YLTKNGYYPIWKHZ-ACZMJKKPSA-N Ala-Ala-Glu Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O YLTKNGYYPIWKHZ-ACZMJKKPSA-N 0.000 description 6
- HOVPGJUNRLMIOZ-CIUDSAMLSA-N Ala-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N HOVPGJUNRLMIOZ-CIUDSAMLSA-N 0.000 description 6
- QUMKPKWYDVMGNT-NUMRIWBASA-N Asn-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QUMKPKWYDVMGNT-NUMRIWBASA-N 0.000 description 6
- QOXDAWODGSIDDI-GUBZILKMSA-N Glu-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N QOXDAWODGSIDDI-GUBZILKMSA-N 0.000 description 6
- OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 description 6
- IMRNSEPSPFQNHF-STQMWFEESA-N Gly-Ser-Trp Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)O IMRNSEPSPFQNHF-STQMWFEESA-N 0.000 description 6
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 6
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 6
- HMZPYMSEAALNAE-ULQDDVLXSA-N Lys-Val-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O HMZPYMSEAALNAE-ULQDDVLXSA-N 0.000 description 6
- OXHSZBRPUGNMKW-DCAQKATOSA-N Met-Gln-Arg Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OXHSZBRPUGNMKW-DCAQKATOSA-N 0.000 description 6
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 6
- AUJWXNGCAQWLEI-KBPBESRZSA-N Phe-Lys-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O AUJWXNGCAQWLEI-KBPBESRZSA-N 0.000 description 6
- SXMSEHDMNIUTSP-DCAQKATOSA-N Pro-Lys-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O SXMSEHDMNIUTSP-DCAQKATOSA-N 0.000 description 6
- BVRBCQBUNGAWFP-KKUMJFAQSA-N Pro-Tyr-Gln Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O BVRBCQBUNGAWFP-KKUMJFAQSA-N 0.000 description 6
- PZHJLTWGMYERRJ-SRVKXCTJSA-N Ser-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)O PZHJLTWGMYERRJ-SRVKXCTJSA-N 0.000 description 6
- 108010068380 arginylarginine Proteins 0.000 description 6
- 108010062796 arginyllysine Proteins 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 108010051110 tyrosyl-lysine Proteins 0.000 description 6
- RGQCNKIDEQJEBT-CQDKDKBSSA-N Ala-Leu-Tyr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 RGQCNKIDEQJEBT-CQDKDKBSSA-N 0.000 description 5
- VRTOMXFZHGWHIJ-KZVJFYERSA-N Ala-Thr-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VRTOMXFZHGWHIJ-KZVJFYERSA-N 0.000 description 5
- UISQLSIBJKEJSS-GUBZILKMSA-N Arg-Arg-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(O)=O UISQLSIBJKEJSS-GUBZILKMSA-N 0.000 description 5
- SPIPSJXLZVTXJL-ZLUOBGJFSA-N Asn-Cys-Ser Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O SPIPSJXLZVTXJL-ZLUOBGJFSA-N 0.000 description 5
- NNMUHYLAYUSTTN-FXQIFTODSA-N Asn-Gln-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O NNMUHYLAYUSTTN-FXQIFTODSA-N 0.000 description 5
- LGCVSPFCFXWUEY-IHPCNDPISA-N Asn-Trp-Tyr Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)O)NC(=O)[C@H](CC(=O)N)N LGCVSPFCFXWUEY-IHPCNDPISA-N 0.000 description 5
- BKXPJCBEHWFSTF-ACZMJKKPSA-N Asp-Gln-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O BKXPJCBEHWFSTF-ACZMJKKPSA-N 0.000 description 5
- SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 5
- IRDBEBCCTCNXGZ-AVGNSLFASA-N Cys-Tyr-Gln Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N)O IRDBEBCCTCNXGZ-AVGNSLFASA-N 0.000 description 5
- DITJVHONFRJKJW-BPUTZDHNSA-N Gln-Trp-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N DITJVHONFRJKJW-BPUTZDHNSA-N 0.000 description 5
- XNOWYPDMSLSRKP-GUBZILKMSA-N Glu-Met-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(O)=O XNOWYPDMSLSRKP-GUBZILKMSA-N 0.000 description 5
- DAHLWSFUXOHMIA-FXQIFTODSA-N Glu-Ser-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O DAHLWSFUXOHMIA-FXQIFTODSA-N 0.000 description 5
- WNGVUZWBXZKQES-YUMQZZPRSA-N Leu-Ala-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O WNGVUZWBXZKQES-YUMQZZPRSA-N 0.000 description 5
- DPWGZWUMUUJQDT-IUCAKERBSA-N Leu-Gln-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O DPWGZWUMUUJQDT-IUCAKERBSA-N 0.000 description 5
- LZHJZLHSRGWBBE-IHRRRGAJSA-N Leu-Lys-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LZHJZLHSRGWBBE-IHRRRGAJSA-N 0.000 description 5
- SBANPBVRHYIMRR-GARJFASQSA-N Leu-Ser-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N SBANPBVRHYIMRR-GARJFASQSA-N 0.000 description 5
- GPJGFSFYBJGYRX-YUMQZZPRSA-N Lys-Gly-Asp Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O GPJGFSFYBJGYRX-YUMQZZPRSA-N 0.000 description 5
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 5
- SWXSLPHTJVAWDF-VEVYYDQMSA-N Pro-Asn-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SWXSLPHTJVAWDF-VEVYYDQMSA-N 0.000 description 5
- QDDJNKWPTJHROJ-UFYCRDLUSA-N Pro-Tyr-Tyr Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H]1NCCC1)C1=CC=C(O)C=C1 QDDJNKWPTJHROJ-UFYCRDLUSA-N 0.000 description 5
- UCOYFSCEIWQYNL-FXQIFTODSA-N Ser-Cys-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(O)=O UCOYFSCEIWQYNL-FXQIFTODSA-N 0.000 description 5
- HXPNJVLVHKABMJ-KKUMJFAQSA-N Ser-Tyr-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CO)N)O HXPNJVLVHKABMJ-KKUMJFAQSA-N 0.000 description 5
- BONYBFXWMXBAND-GQGQLFGLSA-N Trp-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N BONYBFXWMXBAND-GQGQLFGLSA-N 0.000 description 5
- RERRMBXDSFMBQE-ZFWWWQNUSA-N Trp-Met-Gly Chemical compound CSCC[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N RERRMBXDSFMBQE-ZFWWWQNUSA-N 0.000 description 5
- ILTXFANLDMJWPR-SIUGBPQLSA-N Tyr-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N ILTXFANLDMJWPR-SIUGBPQLSA-N 0.000 description 5
- GITNQBVCEQBDQC-KKUMJFAQSA-N Tyr-Lys-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O GITNQBVCEQBDQC-KKUMJFAQSA-N 0.000 description 5
- NHOVZGFNTGMYMI-KKUMJFAQSA-N Tyr-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NHOVZGFNTGMYMI-KKUMJFAQSA-N 0.000 description 5
- DLMNFMXSNGTSNJ-PYJNHQTQSA-N Val-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](C(C)C)N DLMNFMXSNGTSNJ-PYJNHQTQSA-N 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 108010060035 arginylproline Proteins 0.000 description 5
- 108010050848 glycylleucine Proteins 0.000 description 5
- 108010044348 lysyl-glutamyl-aspartic acid Proteins 0.000 description 5
- 108010064235 lysylglycine Proteins 0.000 description 5
- 108010029020 prolylglycine Proteins 0.000 description 5
- 108010090894 prolylleucine Proteins 0.000 description 5
- BRPMXFSTKXXNHF-IUCAKERBSA-N (2s)-1-[2-[[(2s)-pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H]1NCCC1 BRPMXFSTKXXNHF-IUCAKERBSA-N 0.000 description 4
- VENMDXUVHSKEIN-GUBZILKMSA-N Arg-Ser-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VENMDXUVHSKEIN-GUBZILKMSA-N 0.000 description 4
- PZXPWHFYZXTFBI-YUMQZZPRSA-N Asp-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O PZXPWHFYZXTFBI-YUMQZZPRSA-N 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- KKCJHBXMYYVWMX-KQXIARHKSA-N Gln-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N KKCJHBXMYYVWMX-KQXIARHKSA-N 0.000 description 4
- BIAKMWKJMQLZOJ-ZKWXMUAHSA-N His-Ala-Ala Chemical compound C[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1cnc[nH]1)C(O)=O BIAKMWKJMQLZOJ-ZKWXMUAHSA-N 0.000 description 4
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 description 4
- AJLVKXCNXIJHDV-CIUDSAMLSA-N Pro-Ala-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O AJLVKXCNXIJHDV-CIUDSAMLSA-N 0.000 description 4
- VTFXTWDFPTWNJY-RHYQMDGZSA-N Pro-Leu-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VTFXTWDFPTWNJY-RHYQMDGZSA-N 0.000 description 4
- VMLONWHIORGALA-SRVKXCTJSA-N Ser-Leu-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]([NH3+])CO VMLONWHIORGALA-SRVKXCTJSA-N 0.000 description 4
- ZESGVALRVJIVLZ-VFCFLDTKSA-N Thr-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O ZESGVALRVJIVLZ-VFCFLDTKSA-N 0.000 description 4
- SCZJKZLFSSPJDP-ACRUOGEOSA-N Tyr-Phe-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O SCZJKZLFSSPJDP-ACRUOGEOSA-N 0.000 description 4
- CPTQYHDSVGVGDZ-UKJIMTQDSA-N Val-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N CPTQYHDSVGVGDZ-UKJIMTQDSA-N 0.000 description 4
- 108010044940 alanylglutamine Proteins 0.000 description 4
- 108010078144 glutaminyl-glycine Proteins 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 108010017391 lysylvaline Proteins 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 108010065135 phenylalanyl-phenylalanyl-phenylalanine Proteins 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 3
- UCIYCBSJBQGDGM-LPEHRKFASA-N Ala-Arg-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N UCIYCBSJBQGDGM-LPEHRKFASA-N 0.000 description 3
- FUSPCLTUKXQREV-ACZMJKKPSA-N Ala-Glu-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O FUSPCLTUKXQREV-ACZMJKKPSA-N 0.000 description 3
- OMDNCNKNEGFOMM-BQBZGAKWSA-N Ala-Met-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O OMDNCNKNEGFOMM-BQBZGAKWSA-N 0.000 description 3
- HQIZDMIGUJOSNI-IUCAKERBSA-N Arg-Gly-Arg Chemical compound N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O HQIZDMIGUJOSNI-IUCAKERBSA-N 0.000 description 3
- YFHATWYGAAXQCF-JYJNAYRXSA-N Arg-Pro-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YFHATWYGAAXQCF-JYJNAYRXSA-N 0.000 description 3
- OWSMKCJUBAPHED-JYJNAYRXSA-N Arg-Pro-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OWSMKCJUBAPHED-JYJNAYRXSA-N 0.000 description 3
- WCRQQIPFSXFIRN-LPEHRKFASA-N Asn-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N WCRQQIPFSXFIRN-LPEHRKFASA-N 0.000 description 3
- 102000008096 B7-H1 Antigen Human genes 0.000 description 3
- XJKAKYXMFHUIHT-AUTRQRHGSA-N Gln-Glu-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N XJKAKYXMFHUIHT-AUTRQRHGSA-N 0.000 description 3
- DSPQRJXOIXHOHK-WDSKDSINSA-N Glu-Asp-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O DSPQRJXOIXHOHK-WDSKDSINSA-N 0.000 description 3
- QQLBPVKLJBAXBS-FXQIFTODSA-N Glu-Glu-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O QQLBPVKLJBAXBS-FXQIFTODSA-N 0.000 description 3
- DNPCBMNFQVTHMA-DCAQKATOSA-N Glu-Leu-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O DNPCBMNFQVTHMA-DCAQKATOSA-N 0.000 description 3
- TZOVVRJYUDETQG-RCOVLWMOSA-N Gly-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CN TZOVVRJYUDETQG-RCOVLWMOSA-N 0.000 description 3
- DHDOADIPGZTAHT-YUMQZZPRSA-N Gly-Glu-Arg Chemical compound NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N DHDOADIPGZTAHT-YUMQZZPRSA-N 0.000 description 3
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 3
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 3
- VCYVLFAWCJRXFT-HJPIBITLSA-N Ile-Cys-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N VCYVLFAWCJRXFT-HJPIBITLSA-N 0.000 description 3
- BEWFWZRGBDVXRP-PEFMBERDSA-N Ile-Glu-Asn Chemical compound [H]N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O BEWFWZRGBDVXRP-PEFMBERDSA-N 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- IBMVEYRWAWIOTN-RWMBFGLXSA-N Leu-Arg-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(O)=O IBMVEYRWAWIOTN-RWMBFGLXSA-N 0.000 description 3
- LFSQWRSVPNKJGP-WDCWCFNPSA-N Leu-Thr-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCC(O)=O LFSQWRSVPNKJGP-WDCWCFNPSA-N 0.000 description 3
- NCVJJAJVWILAGI-SRVKXCTJSA-N Met-Gln-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N NCVJJAJVWILAGI-SRVKXCTJSA-N 0.000 description 3
- LNLNHXIQPGKRJQ-SRVKXCTJSA-N Pro-Arg-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1 LNLNHXIQPGKRJQ-SRVKXCTJSA-N 0.000 description 3
- AFXCXDQNRXTSBD-FJXKBIBVSA-N Pro-Gly-Thr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O AFXCXDQNRXTSBD-FJXKBIBVSA-N 0.000 description 3
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 3
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 3
- NAXBBCLCEOTAIG-RHYQMDGZSA-N Thr-Arg-Lys Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CCCCN)C(O)=O NAXBBCLCEOTAIG-RHYQMDGZSA-N 0.000 description 3
- QILPDQCTQZDHFM-HJGDQZAQSA-N Thr-Gln-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QILPDQCTQZDHFM-HJGDQZAQSA-N 0.000 description 3
- DVIIYMVCSUQOJG-QEJZJMRPSA-N Trp-Glu-Asp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O DVIIYMVCSUQOJG-QEJZJMRPSA-N 0.000 description 3
- CRCHQCUINSOGFD-JBACZVJFSA-N Trp-Tyr-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N CRCHQCUINSOGFD-JBACZVJFSA-N 0.000 description 3
- IYHNBRUWVBIVJR-IHRRRGAJSA-N Tyr-Gln-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 IYHNBRUWVBIVJR-IHRRRGAJSA-N 0.000 description 3
- SFSZDJHNAICYSD-PMVMPFDFSA-N Tyr-His-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC3=CN=CN3)NC(=O)[C@H](CC4=CC=C(C=C4)O)N SFSZDJHNAICYSD-PMVMPFDFSA-N 0.000 description 3
- JAKHAONCJJZVHT-DCAQKATOSA-N Val-Lys-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N JAKHAONCJJZVHT-DCAQKATOSA-N 0.000 description 3
- GBIUHAYJGWVNLN-UHFFFAOYSA-N Val-Ser-Pro Natural products CC(C)C(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O GBIUHAYJGWVNLN-UHFFFAOYSA-N 0.000 description 3
- HTONZBWRYUKUKC-RCWTZXSCSA-N Val-Thr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HTONZBWRYUKUKC-RCWTZXSCSA-N 0.000 description 3
- 108010087924 alanylproline Proteins 0.000 description 3
- 108010077245 asparaginyl-proline Proteins 0.000 description 3
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 108010079547 glutamylmethionine Proteins 0.000 description 3
- 108010015792 glycyllysine Proteins 0.000 description 3
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 3
- 108010034529 leucyl-lysine Proteins 0.000 description 3
- 108010009298 lysylglutamic acid Proteins 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 108010020532 tyrosyl-proline Proteins 0.000 description 3
- 108010003137 tyrosyltyrosine Proteins 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 2
- LGFCAXJBAZESCF-ACZMJKKPSA-N Ala-Gln-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O LGFCAXJBAZESCF-ACZMJKKPSA-N 0.000 description 2
- ZODMADSIQZZBSQ-FXQIFTODSA-N Ala-Gln-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZODMADSIQZZBSQ-FXQIFTODSA-N 0.000 description 2
- VGPWRRFOPXVGOH-BYPYZUCNSA-N Ala-Gly-Gly Chemical compound C[C@H](N)C(=O)NCC(=O)NCC(O)=O VGPWRRFOPXVGOH-BYPYZUCNSA-N 0.000 description 2
- RUXQNKVQSKOOBS-JURCDPSOSA-N Ala-Phe-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RUXQNKVQSKOOBS-JURCDPSOSA-N 0.000 description 2
- DXTYEWAQOXYRHZ-KKXDTOCCSA-N Ala-Phe-Tyr Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O)N DXTYEWAQOXYRHZ-KKXDTOCCSA-N 0.000 description 2
- ADSGHMXEAZJJNF-DCAQKATOSA-N Ala-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N ADSGHMXEAZJJNF-DCAQKATOSA-N 0.000 description 2
- FFZJHQODAYHGPO-KZVJFYERSA-N Ala-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N FFZJHQODAYHGPO-KZVJFYERSA-N 0.000 description 2
- AUFACLFHBAGZEN-ZLUOBGJFSA-N Ala-Ser-Cys Chemical compound N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O AUFACLFHBAGZEN-ZLUOBGJFSA-N 0.000 description 2
- XQNRANMFRPCFFW-GCJQMDKQSA-N Ala-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C)N)O XQNRANMFRPCFFW-GCJQMDKQSA-N 0.000 description 2
- CLOMBHBBUKAUBP-LSJOCFKGSA-N Ala-Val-His Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N CLOMBHBBUKAUBP-LSJOCFKGSA-N 0.000 description 2
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 2
- 108090000672 Annexin A5 Proteins 0.000 description 2
- 102000004121 Annexin A5 Human genes 0.000 description 2
- OQCWXQJLCDPRHV-UWVGGRQHSA-N Arg-Gly-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O OQCWXQJLCDPRHV-UWVGGRQHSA-N 0.000 description 2
- BSYKSCBTTQKOJG-GUBZILKMSA-N Arg-Pro-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O BSYKSCBTTQKOJG-GUBZILKMSA-N 0.000 description 2
- WKPXXXUSUHAXDE-SRVKXCTJSA-N Arg-Pro-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O WKPXXXUSUHAXDE-SRVKXCTJSA-N 0.000 description 2
- ADPACBMPYWJJCE-FXQIFTODSA-N Arg-Ser-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O ADPACBMPYWJJCE-FXQIFTODSA-N 0.000 description 2
- ICRHGPYYXMWHIE-LPEHRKFASA-N Arg-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ICRHGPYYXMWHIE-LPEHRKFASA-N 0.000 description 2
- ZUVMUOOHJYNJPP-XIRDDKMYSA-N Arg-Trp-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZUVMUOOHJYNJPP-XIRDDKMYSA-N 0.000 description 2
- XWGJDUSDTRPQRK-ZLUOBGJFSA-N Asn-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O XWGJDUSDTRPQRK-ZLUOBGJFSA-N 0.000 description 2
- CZIXHXIJJZLYRJ-SRVKXCTJSA-N Asn-Cys-Tyr Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CZIXHXIJJZLYRJ-SRVKXCTJSA-N 0.000 description 2
- OLGCWMNDJTWQAG-GUBZILKMSA-N Asn-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(N)=O OLGCWMNDJTWQAG-GUBZILKMSA-N 0.000 description 2
- CLUMZOKVGUWUFD-CIUDSAMLSA-N Asp-Leu-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O CLUMZOKVGUWUFD-CIUDSAMLSA-N 0.000 description 2
- CJUKAWUWBZCTDQ-SRVKXCTJSA-N Asp-Leu-Lys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O CJUKAWUWBZCTDQ-SRVKXCTJSA-N 0.000 description 2
- GYWQGGUCMDCUJE-DLOVCJGASA-N Asp-Phe-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O GYWQGGUCMDCUJE-DLOVCJGASA-N 0.000 description 2
- NOCCABSVTRONIN-CIUDSAMLSA-N Cys-Ala-Leu Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CS)N NOCCABSVTRONIN-CIUDSAMLSA-N 0.000 description 2
- WDQXKVCQXRNOSI-GHCJXIJMSA-N Cys-Asp-Ile Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WDQXKVCQXRNOSI-GHCJXIJMSA-N 0.000 description 2
- QJUDRFBUWAGUSG-SRVKXCTJSA-N Cys-Cys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)N QJUDRFBUWAGUSG-SRVKXCTJSA-N 0.000 description 2
- SWJYSDXMTPMBHO-FXQIFTODSA-N Cys-Pro-Ser Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O SWJYSDXMTPMBHO-FXQIFTODSA-N 0.000 description 2
- BCWIFCLVCRAIQK-ZLUOBGJFSA-N Cys-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)O BCWIFCLVCRAIQK-ZLUOBGJFSA-N 0.000 description 2
- NXQCSPVUPLUTJH-WHFBIAKZSA-N Cys-Ser-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O NXQCSPVUPLUTJH-WHFBIAKZSA-N 0.000 description 2
- DQGIAOGALAQBGK-BWBBJGPYSA-N Cys-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N)O DQGIAOGALAQBGK-BWBBJGPYSA-N 0.000 description 2
- 206010050685 Cytokine storm Diseases 0.000 description 2
- LTLXPHKSQQILNF-CIUDSAMLSA-N Gln-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)N)N)CN=C(N)N LTLXPHKSQQILNF-CIUDSAMLSA-N 0.000 description 2
- MWLYSLMKFXWZPW-ZPFDUUQYSA-N Gln-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CCC(N)=O MWLYSLMKFXWZPW-ZPFDUUQYSA-N 0.000 description 2
- DTMLKCYOQKZXKZ-HJGDQZAQSA-N Gln-Arg-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DTMLKCYOQKZXKZ-HJGDQZAQSA-N 0.000 description 2
- CLPQUWHBWXFJOX-BQBZGAKWSA-N Gln-Gly-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O CLPQUWHBWXFJOX-BQBZGAKWSA-N 0.000 description 2
- XQDGOJPVMSWZSO-SRVKXCTJSA-N Gln-Pro-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)N)N XQDGOJPVMSWZSO-SRVKXCTJSA-N 0.000 description 2
- UTOQQOMEJDPDMX-ACZMJKKPSA-N Gln-Ser-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O UTOQQOMEJDPDMX-ACZMJKKPSA-N 0.000 description 2
- UTKICHUQEQBDGC-ACZMJKKPSA-N Glu-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N UTKICHUQEQBDGC-ACZMJKKPSA-N 0.000 description 2
- VAIWPXWHWAPYDF-FXQIFTODSA-N Glu-Asp-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O VAIWPXWHWAPYDF-FXQIFTODSA-N 0.000 description 2
- PXXGVUVQWQGGIG-YUMQZZPRSA-N Glu-Gly-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N PXXGVUVQWQGGIG-YUMQZZPRSA-N 0.000 description 2
- RXESHTOTINOODU-JYJNAYRXSA-N Glu-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCC(=O)O)N RXESHTOTINOODU-JYJNAYRXSA-N 0.000 description 2
- HMJULNMJWOZNFI-XHNCKOQMSA-N Glu-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)N)C(=O)O HMJULNMJWOZNFI-XHNCKOQMSA-N 0.000 description 2
- SUDUYJOBLHQAMI-WHFBIAKZSA-N Gly-Asp-Cys Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(O)=O SUDUYJOBLHQAMI-WHFBIAKZSA-N 0.000 description 2
- NSTUFLGQJCOCDL-UWVGGRQHSA-N Gly-Leu-Arg Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NSTUFLGQJCOCDL-UWVGGRQHSA-N 0.000 description 2
- VNNRLUNBJSWZPF-ZKWXMUAHSA-N Gly-Ser-Ile Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNNRLUNBJSWZPF-ZKWXMUAHSA-N 0.000 description 2
- HDOYNXLPTRQLAD-JBDRJPRFSA-N Ile-Ala-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)O)N HDOYNXLPTRQLAD-JBDRJPRFSA-N 0.000 description 2
- IPYVXYDYLHVWHU-GMOBBJLQSA-N Ile-Asn-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCSC)C(=O)O)N IPYVXYDYLHVWHU-GMOBBJLQSA-N 0.000 description 2
- SJLVSMMIFYTSGY-GRLWGSQLSA-N Ile-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N SJLVSMMIFYTSGY-GRLWGSQLSA-N 0.000 description 2
- GVKKVHNRTUFCCE-BJDJZHNGSA-N Ile-Leu-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)O)N GVKKVHNRTUFCCE-BJDJZHNGSA-N 0.000 description 2
- KLJKJVXDHVUMMZ-KKPKCPPISA-N Ile-Phe-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)O)N KLJKJVXDHVUMMZ-KKPKCPPISA-N 0.000 description 2
- ZSESFIFAYQEKRD-CYDGBPFRSA-N Ile-Val-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(=O)O)N ZSESFIFAYQEKRD-CYDGBPFRSA-N 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- IIKJNQWOQIWWMR-CIUDSAMLSA-N Leu-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)N IIKJNQWOQIWWMR-CIUDSAMLSA-N 0.000 description 2
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 description 2
- ZGUMORRUBUCXEH-AVGNSLFASA-N Leu-Lys-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZGUMORRUBUCXEH-AVGNSLFASA-N 0.000 description 2
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 2
- LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 description 2
- LMDVGHQPPPLYAR-IHRRRGAJSA-N Leu-Val-His Chemical compound N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O LMDVGHQPPPLYAR-IHRRRGAJSA-N 0.000 description 2
- ABHIXYDMILIUKV-CIUDSAMLSA-N Lys-Asn-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ABHIXYDMILIUKV-CIUDSAMLSA-N 0.000 description 2
- JBRWKVANRYPCAF-XIRDDKMYSA-N Lys-Asn-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N JBRWKVANRYPCAF-XIRDDKMYSA-N 0.000 description 2
- NNKLKUUGESXCBS-KBPBESRZSA-N Lys-Gly-Tyr Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O NNKLKUUGESXCBS-KBPBESRZSA-N 0.000 description 2
- OWRUUFUVXFREBD-KKUMJFAQSA-N Lys-His-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O OWRUUFUVXFREBD-KKUMJFAQSA-N 0.000 description 2
- PINHPJWGVBKQII-SRVKXCTJSA-N Lys-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N PINHPJWGVBKQII-SRVKXCTJSA-N 0.000 description 2
- DBOMZJOESVYERT-GUBZILKMSA-N Met-Asn-Met Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCSC)C(=O)O)N DBOMZJOESVYERT-GUBZILKMSA-N 0.000 description 2
- MYAPQOBHGWJZOM-UWVGGRQHSA-N Met-Gly-Leu Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C MYAPQOBHGWJZOM-UWVGGRQHSA-N 0.000 description 2
- MHQXIBRPDKXDGZ-ZFWWWQNUSA-N Met-Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CNC(=O)[C@@H](N)CCSC)C(O)=O)=CNC2=C1 MHQXIBRPDKXDGZ-ZFWWWQNUSA-N 0.000 description 2
- VSJAPSMRFYUOKS-IUCAKERBSA-N Met-Pro-Gly Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O VSJAPSMRFYUOKS-IUCAKERBSA-N 0.000 description 2
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 2
- 239000012124 Opti-MEM Substances 0.000 description 2
- CBENHWCORLVGEQ-HJOGWXRNSA-N Phe-Phe-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CBENHWCORLVGEQ-HJOGWXRNSA-N 0.000 description 2
- UNBFGVQVQGXXCK-KKUMJFAQSA-N Phe-Ser-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O UNBFGVQVQGXXCK-KKUMJFAQSA-N 0.000 description 2
- ICTZKEXYDDZZFP-SRVKXCTJSA-N Pro-Arg-Pro Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCCN1 ICTZKEXYDDZZFP-SRVKXCTJSA-N 0.000 description 2
- DRKAXLDECUGLFE-ULQDDVLXSA-N Pro-Leu-Phe Chemical compound CC(C)C[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O DRKAXLDECUGLFE-ULQDDVLXSA-N 0.000 description 2
- BUEIYHBJHCDAMI-UFYCRDLUSA-N Pro-Phe-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O BUEIYHBJHCDAMI-UFYCRDLUSA-N 0.000 description 2
- JLMZKEQFMVORMA-SRVKXCTJSA-N Pro-Pro-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 JLMZKEQFMVORMA-SRVKXCTJSA-N 0.000 description 2
- SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 2
- AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 2
- JXVXYRZQIUPYSA-NHCYSSNCSA-N Pro-Val-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JXVXYRZQIUPYSA-NHCYSSNCSA-N 0.000 description 2
- FHJQROWZEJFZPO-SRVKXCTJSA-N Pro-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FHJQROWZEJFZPO-SRVKXCTJSA-N 0.000 description 2
- VAUMZJHYZQXZBQ-WHFBIAKZSA-N Ser-Asn-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O VAUMZJHYZQXZBQ-WHFBIAKZSA-N 0.000 description 2
- CTRHXXXHUJTTRZ-ZLUOBGJFSA-N Ser-Asp-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)C(=O)O CTRHXXXHUJTTRZ-ZLUOBGJFSA-N 0.000 description 2
- HEQPKICPPDOSIN-SRVKXCTJSA-N Ser-Asp-Tyr Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HEQPKICPPDOSIN-SRVKXCTJSA-N 0.000 description 2
- MOVJSUIKUNCVMG-ZLUOBGJFSA-N Ser-Cys-Ser Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)O)N)O MOVJSUIKUNCVMG-ZLUOBGJFSA-N 0.000 description 2
- CRZRTKAVUUGKEQ-ACZMJKKPSA-N Ser-Gln-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O CRZRTKAVUUGKEQ-ACZMJKKPSA-N 0.000 description 2
- VZQRNAYURWAEFE-KKUMJFAQSA-N Ser-Leu-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 VZQRNAYURWAEFE-KKUMJFAQSA-N 0.000 description 2
- HDBOEVPDIDDEPC-CIUDSAMLSA-N Ser-Lys-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O HDBOEVPDIDDEPC-CIUDSAMLSA-N 0.000 description 2
- GVMUJUPXFQFBBZ-GUBZILKMSA-N Ser-Lys-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GVMUJUPXFQFBBZ-GUBZILKMSA-N 0.000 description 2
- RHAPJNVNWDBFQI-BQBZGAKWSA-N Ser-Pro-Gly Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O RHAPJNVNWDBFQI-BQBZGAKWSA-N 0.000 description 2
- BDMWLJLPPUCLNV-XGEHTFHBSA-N Ser-Thr-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BDMWLJLPPUCLNV-XGEHTFHBSA-N 0.000 description 2
- FZNNGIHSIPKFRE-QEJZJMRPSA-N Ser-Trp-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(O)=O FZNNGIHSIPKFRE-QEJZJMRPSA-N 0.000 description 2
- NYQIZWROIMIQSL-VEVYYDQMSA-N Thr-Pro-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O NYQIZWROIMIQSL-VEVYYDQMSA-N 0.000 description 2
- KZTLZZQTJMCGIP-ZJDVBMNYSA-N Thr-Val-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KZTLZZQTJMCGIP-ZJDVBMNYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- AYHSJESDFKREAR-KKUMJFAQSA-N Tyr-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AYHSJESDFKREAR-KKUMJFAQSA-N 0.000 description 2
- NXRGXTBPMOGFID-CFMVVWHZSA-N Tyr-Ile-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O NXRGXTBPMOGFID-CFMVVWHZSA-N 0.000 description 2
- LQGDFDYGDQEMGA-PXDAIIFMSA-N Tyr-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N LQGDFDYGDQEMGA-PXDAIIFMSA-N 0.000 description 2
- BSCBBPKDVOZICB-KKUMJFAQSA-N Tyr-Leu-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O BSCBBPKDVOZICB-KKUMJFAQSA-N 0.000 description 2
- QVYFTFIBKCDHIE-ACRUOGEOSA-N Tyr-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCCN)C(=O)O)N)O QVYFTFIBKCDHIE-ACRUOGEOSA-N 0.000 description 2
- DIOSYUIWOQCXNR-ONGXEEELSA-N Val-Lys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O DIOSYUIWOQCXNR-ONGXEEELSA-N 0.000 description 2
- GTACFKZDQFTVAI-STECZYCISA-N Val-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)CC1=CC=C(O)C=C1 GTACFKZDQFTVAI-STECZYCISA-N 0.000 description 2
- 238000011467 adoptive cell therapy Methods 0.000 description 2
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 108010013835 arginine glutamate Proteins 0.000 description 2
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 206010052015 cytokine release syndrome Diseases 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 108010027668 glycyl-alanyl-valine Proteins 0.000 description 2
- 108010050475 glycyl-leucyl-tyrosine Proteins 0.000 description 2
- 108010089804 glycyl-threonine Proteins 0.000 description 2
- 108010037850 glycylvaline Proteins 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 108010018006 histidylserine Proteins 0.000 description 2
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 2
- 108010057821 leucylproline Proteins 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 108010005942 methionylglycine Proteins 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 108010014614 prolyl-glycyl-proline Proteins 0.000 description 2
- 108010077112 prolyl-proline Proteins 0.000 description 2
- 108010079317 prolyl-tyrosine Proteins 0.000 description 2
- 108010073969 valyllysine Proteins 0.000 description 2
- PIDRBUDUWHBYSR-UHFFFAOYSA-N 1-[2-[[2-[(2-amino-4-methylpentanoyl)amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O PIDRBUDUWHBYSR-UHFFFAOYSA-N 0.000 description 1
- BUANFPRKJKJSRR-ACZMJKKPSA-N Ala-Ala-Gln Chemical compound C[C@H]([NH3+])C(=O)N[C@@H](C)C(=O)N[C@H](C([O-])=O)CCC(N)=O BUANFPRKJKJSRR-ACZMJKKPSA-N 0.000 description 1
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 1
- NHCPCLJZRSIDHS-ZLUOBGJFSA-N Ala-Asp-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O NHCPCLJZRSIDHS-ZLUOBGJFSA-N 0.000 description 1
- WJRXVTCKASUIFF-FXQIFTODSA-N Ala-Cys-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WJRXVTCKASUIFF-FXQIFTODSA-N 0.000 description 1
- YEELWQSXYBJVSV-UWJYBYFXSA-N Ala-Cys-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YEELWQSXYBJVSV-UWJYBYFXSA-N 0.000 description 1
- CJQAEJMHBAOQHA-DLOVCJGASA-N Ala-Phe-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)N)C(=O)O)N CJQAEJMHBAOQHA-DLOVCJGASA-N 0.000 description 1
- ZBLQIYPCUWZSRZ-QEJZJMRPSA-N Ala-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 ZBLQIYPCUWZSRZ-QEJZJMRPSA-N 0.000 description 1
- NZGRHTKZFSVPAN-BIIVOSGPSA-N Ala-Ser-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N NZGRHTKZFSVPAN-BIIVOSGPSA-N 0.000 description 1
- VNFSAYFQLXPHPY-CIQUZCHMSA-N Ala-Thr-Ile Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNFSAYFQLXPHPY-CIQUZCHMSA-N 0.000 description 1
- DHONNEYAZPNGSG-UBHSHLNASA-N Ala-Val-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 DHONNEYAZPNGSG-UBHSHLNASA-N 0.000 description 1
- ZDILXFDENZVOTL-BPNCWPANSA-N Ala-Val-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZDILXFDENZVOTL-BPNCWPANSA-N 0.000 description 1
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 1
- PQWTZSNVWSOFFK-FXQIFTODSA-N Arg-Asp-Asn Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)CN=C(N)N PQWTZSNVWSOFFK-FXQIFTODSA-N 0.000 description 1
- RKRSYHCNPFGMTA-CIUDSAMLSA-N Arg-Glu-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O RKRSYHCNPFGMTA-CIUDSAMLSA-N 0.000 description 1
- AQPVUEJJARLJHB-BQBZGAKWSA-N Arg-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N AQPVUEJJARLJHB-BQBZGAKWSA-N 0.000 description 1
- ZZZWQALDSQQBEW-STQMWFEESA-N Arg-Gly-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ZZZWQALDSQQBEW-STQMWFEESA-N 0.000 description 1
- CRCCTGPNZUCAHE-DCAQKATOSA-N Arg-His-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CC1=CN=CN1 CRCCTGPNZUCAHE-DCAQKATOSA-N 0.000 description 1
- LLUGJARLJCGLAR-CYDGBPFRSA-N Arg-Ile-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N LLUGJARLJCGLAR-CYDGBPFRSA-N 0.000 description 1
- RIIVUOJDDQXHRV-SRVKXCTJSA-N Arg-Lys-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O RIIVUOJDDQXHRV-SRVKXCTJSA-N 0.000 description 1
- DIIGDGJKTMLQQW-IHRRRGAJSA-N Arg-Lys-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)N DIIGDGJKTMLQQW-IHRRRGAJSA-N 0.000 description 1
- BTJVOUQWFXABOI-IHRRRGAJSA-N Arg-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCNC(N)=N BTJVOUQWFXABOI-IHRRRGAJSA-N 0.000 description 1
- XSPKAHFVDKRGRL-DCAQKATOSA-N Arg-Pro-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XSPKAHFVDKRGRL-DCAQKATOSA-N 0.000 description 1
- 108010051330 Arg-Pro-Gly-Pro Proteins 0.000 description 1
- JJIBHAOBNIFUEL-SRVKXCTJSA-N Arg-Pro-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)N JJIBHAOBNIFUEL-SRVKXCTJSA-N 0.000 description 1
- YCYXHLZRUSJITQ-SRVKXCTJSA-N Arg-Pro-Pro Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 YCYXHLZRUSJITQ-SRVKXCTJSA-N 0.000 description 1
- VUGWHBXPMAHEGZ-SRVKXCTJSA-N Arg-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCN=C(N)N VUGWHBXPMAHEGZ-SRVKXCTJSA-N 0.000 description 1
- JOTRDIXZHNQYGP-DCAQKATOSA-N Arg-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N JOTRDIXZHNQYGP-DCAQKATOSA-N 0.000 description 1
- ULBHWNVWSCJLCO-NHCYSSNCSA-N Arg-Val-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N ULBHWNVWSCJLCO-NHCYSSNCSA-N 0.000 description 1
- WOZDCBHUGJVJPL-AVGNSLFASA-N Arg-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N WOZDCBHUGJVJPL-AVGNSLFASA-N 0.000 description 1
- YNSCBOUZTAGIGO-ZLUOBGJFSA-N Asn-Asn-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N)C(=O)N YNSCBOUZTAGIGO-ZLUOBGJFSA-N 0.000 description 1
- PAXHINASXXXILC-SRVKXCTJSA-N Asn-Asp-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N)O PAXHINASXXXILC-SRVKXCTJSA-N 0.000 description 1
- KZYSHAMXEBPJBD-JRQIVUDYSA-N Asn-Thr-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KZYSHAMXEBPJBD-JRQIVUDYSA-N 0.000 description 1
- RTFXPCYMDYBZNQ-SRVKXCTJSA-N Asn-Tyr-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O RTFXPCYMDYBZNQ-SRVKXCTJSA-N 0.000 description 1
- AMRANMVXQWXNAH-ZLUOBGJFSA-N Asp-Cys-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CC(O)=O AMRANMVXQWXNAH-ZLUOBGJFSA-N 0.000 description 1
- BIVYLQMZPHDUIH-WHFBIAKZSA-N Asp-Gly-Cys Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N)C(=O)O BIVYLQMZPHDUIH-WHFBIAKZSA-N 0.000 description 1
- UZFHNLYQWMGUHU-DCAQKATOSA-N Asp-Lys-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UZFHNLYQWMGUHU-DCAQKATOSA-N 0.000 description 1
- FQHBAQLBIXLWAG-DCAQKATOSA-N Asp-Lys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)N FQHBAQLBIXLWAG-DCAQKATOSA-N 0.000 description 1
- RPUYTJJZXQBWDT-SRVKXCTJSA-N Asp-Phe-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N RPUYTJJZXQBWDT-SRVKXCTJSA-N 0.000 description 1
- GIKOVDMXBAFXDF-NHCYSSNCSA-N Asp-Val-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O GIKOVDMXBAFXDF-NHCYSSNCSA-N 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- AMRLSQGGERHDHJ-FXQIFTODSA-N Cys-Ala-Arg Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AMRLSQGGERHDHJ-FXQIFTODSA-N 0.000 description 1
- CLDCTNHPILWQCW-CIUDSAMLSA-N Cys-Arg-Glu Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N CLDCTNHPILWQCW-CIUDSAMLSA-N 0.000 description 1
- XTHUKRLJRUVVBF-WHFBIAKZSA-N Cys-Gly-Ser Chemical compound SC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O XTHUKRLJRUVVBF-WHFBIAKZSA-N 0.000 description 1
- HJGUQJJJXQGXGJ-FXQIFTODSA-N Cys-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CS)N HJGUQJJJXQGXGJ-FXQIFTODSA-N 0.000 description 1
- XBELMDARIGXDKY-GUBZILKMSA-N Cys-Pro-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)N XBELMDARIGXDKY-GUBZILKMSA-N 0.000 description 1
- NNQHEEQNPQYPGL-FXQIFTODSA-N Gln-Ala-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O NNQHEEQNPQYPGL-FXQIFTODSA-N 0.000 description 1
- KVYVOGYEMPEXBT-GUBZILKMSA-N Gln-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O KVYVOGYEMPEXBT-GUBZILKMSA-N 0.000 description 1
- OYTPNWYZORARHL-XHNCKOQMSA-N Gln-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N OYTPNWYZORARHL-XHNCKOQMSA-N 0.000 description 1
- SHERTACNJPYHAR-ACZMJKKPSA-N Gln-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O SHERTACNJPYHAR-ACZMJKKPSA-N 0.000 description 1
- XOKGKOQWADCLFQ-GARJFASQSA-N Gln-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XOKGKOQWADCLFQ-GARJFASQSA-N 0.000 description 1
- INFBPLSHYFALDE-ACZMJKKPSA-N Gln-Asn-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O INFBPLSHYFALDE-ACZMJKKPSA-N 0.000 description 1
- TWHDOEYLXXQYOZ-FXQIFTODSA-N Gln-Asn-Gln Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N TWHDOEYLXXQYOZ-FXQIFTODSA-N 0.000 description 1
- XEYMBRRKIFYQMF-GUBZILKMSA-N Gln-Asp-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O XEYMBRRKIFYQMF-GUBZILKMSA-N 0.000 description 1
- NVEASDQHBRZPSU-BQBZGAKWSA-N Gln-Gln-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O NVEASDQHBRZPSU-BQBZGAKWSA-N 0.000 description 1
- SNLOOPZHAQDMJG-CIUDSAMLSA-N Gln-Glu-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SNLOOPZHAQDMJG-CIUDSAMLSA-N 0.000 description 1
- PNENQZWRFMUZOM-DCAQKATOSA-N Gln-Glu-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O PNENQZWRFMUZOM-DCAQKATOSA-N 0.000 description 1
- FGYPOQPQTUNESW-IUCAKERBSA-N Gln-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N FGYPOQPQTUNESW-IUCAKERBSA-N 0.000 description 1
- MSHXWFKYXJTLEZ-CIUDSAMLSA-N Gln-Met-Asn Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N MSHXWFKYXJTLEZ-CIUDSAMLSA-N 0.000 description 1
- MQJDLNRXBOELJW-KKUMJFAQSA-N Gln-Pro-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O MQJDLNRXBOELJW-KKUMJFAQSA-N 0.000 description 1
- STHSGOZLFLFGSS-SUSMZKCASA-N Gln-Thr-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O STHSGOZLFLFGSS-SUSMZKCASA-N 0.000 description 1
- RUFHOVYUYSNDNY-ACZMJKKPSA-N Glu-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O RUFHOVYUYSNDNY-ACZMJKKPSA-N 0.000 description 1
- WOSRKEJQESVHGA-CIUDSAMLSA-N Glu-Arg-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O WOSRKEJQESVHGA-CIUDSAMLSA-N 0.000 description 1
- LXAUHIRMWXQRKI-XHNCKOQMSA-N Glu-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N)C(=O)O LXAUHIRMWXQRKI-XHNCKOQMSA-N 0.000 description 1
- SJPMNHCEWPTRBR-BQBZGAKWSA-N Glu-Glu-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O SJPMNHCEWPTRBR-BQBZGAKWSA-N 0.000 description 1
- BUAKRRKDHSSIKK-IHRRRGAJSA-N Glu-Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BUAKRRKDHSSIKK-IHRRRGAJSA-N 0.000 description 1
- LRPXYSGPOBVBEH-IUCAKERBSA-N Glu-Gly-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O LRPXYSGPOBVBEH-IUCAKERBSA-N 0.000 description 1
- GJBUAAAIZSRCDC-GVXVVHGQSA-N Glu-Leu-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O GJBUAAAIZSRCDC-GVXVVHGQSA-N 0.000 description 1
- HQOGXFLBAKJUMH-CIUDSAMLSA-N Glu-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)O)N HQOGXFLBAKJUMH-CIUDSAMLSA-N 0.000 description 1
- HLYCMRDRWGSTPZ-CIUDSAMLSA-N Glu-Pro-Cys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CS)C(=O)O HLYCMRDRWGSTPZ-CIUDSAMLSA-N 0.000 description 1
- WXONSNSSBYQGNN-AVGNSLFASA-N Glu-Ser-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WXONSNSSBYQGNN-AVGNSLFASA-N 0.000 description 1
- QCMVGXDELYMZET-GLLZPBPUSA-N Glu-Thr-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QCMVGXDELYMZET-GLLZPBPUSA-N 0.000 description 1
- YQPFCZVKMUVZIN-AUTRQRHGSA-N Glu-Val-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O YQPFCZVKMUVZIN-AUTRQRHGSA-N 0.000 description 1
- NTNUEBVGKMVANB-NHCYSSNCSA-N Glu-Val-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O NTNUEBVGKMVANB-NHCYSSNCSA-N 0.000 description 1
- PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 1
- JRDYDYXZKFNNRQ-XPUUQOCRSA-N Gly-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN JRDYDYXZKFNNRQ-XPUUQOCRSA-N 0.000 description 1
- UPOJUWHGMDJUQZ-IUCAKERBSA-N Gly-Arg-Arg Chemical compound NC(=N)NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UPOJUWHGMDJUQZ-IUCAKERBSA-N 0.000 description 1
- CLODWIOAKCSBAN-BQBZGAKWSA-N Gly-Arg-Asp Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(O)=O)C(O)=O CLODWIOAKCSBAN-BQBZGAKWSA-N 0.000 description 1
- GWCRIHNSVMOBEQ-BQBZGAKWSA-N Gly-Arg-Ser Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O GWCRIHNSVMOBEQ-BQBZGAKWSA-N 0.000 description 1
- XXGQRGQPGFYECI-WDSKDSINSA-N Gly-Cys-Glu Chemical compound NCC(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCC(O)=O XXGQRGQPGFYECI-WDSKDSINSA-N 0.000 description 1
- DTRUBYPMMVPQPD-YUMQZZPRSA-N Gly-Gln-Arg Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O DTRUBYPMMVPQPD-YUMQZZPRSA-N 0.000 description 1
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 1
- QITBQGJOXQYMOA-ZETCQYMHSA-N Gly-Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CN QITBQGJOXQYMOA-ZETCQYMHSA-N 0.000 description 1
- YTSVAIMKVLZUDU-YUMQZZPRSA-N Gly-Leu-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YTSVAIMKVLZUDU-YUMQZZPRSA-N 0.000 description 1
- AFWYPMDMDYCKMD-KBPBESRZSA-N Gly-Leu-Tyr Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AFWYPMDMDYCKMD-KBPBESRZSA-N 0.000 description 1
- MIIVFRCYJABHTQ-ONGXEEELSA-N Gly-Leu-Val Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O MIIVFRCYJABHTQ-ONGXEEELSA-N 0.000 description 1
- ZWRDOVYMQAAISL-UWVGGRQHSA-N Gly-Met-Lys Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCCN ZWRDOVYMQAAISL-UWVGGRQHSA-N 0.000 description 1
- OCPPBNKYGYSLOE-IUCAKERBSA-N Gly-Pro-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN OCPPBNKYGYSLOE-IUCAKERBSA-N 0.000 description 1
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-N 0.000 description 1
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 1
- ZZWUYQXMIFTIIY-WEDXCCLWSA-N Gly-Thr-Leu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O ZZWUYQXMIFTIIY-WEDXCCLWSA-N 0.000 description 1
- WTUSRDZLLWGYAT-KCTSRDHCSA-N Gly-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)CN WTUSRDZLLWGYAT-KCTSRDHCSA-N 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- DYKZGTLPSNOFHU-DEQVHRJGSA-N His-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N DYKZGTLPSNOFHU-DEQVHRJGSA-N 0.000 description 1
- RXKFKJVJVHLRIE-XIRDDKMYSA-N His-Ser-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CN=CN3)N RXKFKJVJVHLRIE-XIRDDKMYSA-N 0.000 description 1
- FCPSGEVYIVXPPO-QTKMDUPCSA-N His-Thr-Arg Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FCPSGEVYIVXPPO-QTKMDUPCSA-N 0.000 description 1
- WSWAUVHXQREQQG-JYJNAYRXSA-N His-Tyr-Gln Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O WSWAUVHXQREQQG-JYJNAYRXSA-N 0.000 description 1
- 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 description 1
- MKWSZEHGHSLNPF-NAKRPEOUSA-N Ile-Ala-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O)N MKWSZEHGHSLNPF-NAKRPEOUSA-N 0.000 description 1
- QLRMMMQNCWBNPQ-QXEWZRGKSA-N Ile-Arg-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)O)N QLRMMMQNCWBNPQ-QXEWZRGKSA-N 0.000 description 1
- VZIFYHYNQDIPLI-HJWJTTGWSA-N Ile-Arg-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N VZIFYHYNQDIPLI-HJWJTTGWSA-N 0.000 description 1
- SRGRINJFBHKHAC-NAKRPEOUSA-N Ile-Cys-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)O)N SRGRINJFBHKHAC-NAKRPEOUSA-N 0.000 description 1
- HUWYGQOISIJNMK-SIGLWIIPSA-N Ile-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N HUWYGQOISIJNMK-SIGLWIIPSA-N 0.000 description 1
- LRAUKBMYHHNADU-DKIMLUQUSA-N Ile-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)CC)CC1=CC=CC=C1 LRAUKBMYHHNADU-DKIMLUQUSA-N 0.000 description 1
- REXAUQBGSGDEJY-IGISWZIWSA-N Ile-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N REXAUQBGSGDEJY-IGISWZIWSA-N 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 1
- FADYJNXDPBKVCA-UHFFFAOYSA-N L-Phenylalanyl-L-lysin Natural products NCCCCC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FADYJNXDPBKVCA-UHFFFAOYSA-N 0.000 description 1
- JKGHDYGZRDWHGA-SRVKXCTJSA-N Leu-Asn-Leu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JKGHDYGZRDWHGA-SRVKXCTJSA-N 0.000 description 1
- OGCQGUIWMSBHRZ-CIUDSAMLSA-N Leu-Asn-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O OGCQGUIWMSBHRZ-CIUDSAMLSA-N 0.000 description 1
- FIJMQLGQLBLBOL-HJGDQZAQSA-N Leu-Asn-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O FIJMQLGQLBLBOL-HJGDQZAQSA-N 0.000 description 1
- DLCOFDAHNMMQPP-SRVKXCTJSA-N Leu-Asp-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DLCOFDAHNMMQPP-SRVKXCTJSA-N 0.000 description 1
- FQZPTCNSNPWHLJ-AVGNSLFASA-N Leu-Gln-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O FQZPTCNSNPWHLJ-AVGNSLFASA-N 0.000 description 1
- BABSVXFGKFLIGW-UWVGGRQHSA-N Leu-Gly-Arg Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCNC(N)=N BABSVXFGKFLIGW-UWVGGRQHSA-N 0.000 description 1
- VBZOAGIPCULURB-QWRGUYRKSA-N Leu-Gly-His Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N VBZOAGIPCULURB-QWRGUYRKSA-N 0.000 description 1
- MPSBSKHOWJQHBS-IHRRRGAJSA-N Leu-His-Met Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCSC)C(=O)O)N MPSBSKHOWJQHBS-IHRRRGAJSA-N 0.000 description 1
- OMHLATXVNQSALM-FQUUOJAGSA-N Leu-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(C)C)N OMHLATXVNQSALM-FQUUOJAGSA-N 0.000 description 1
- IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 1
- UCNNZELZXFXXJQ-BZSNNMDCSA-N Leu-Leu-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 UCNNZELZXFXXJQ-BZSNNMDCSA-N 0.000 description 1
- BGZCJDGBBUUBHA-KKUMJFAQSA-N Leu-Lys-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O BGZCJDGBBUUBHA-KKUMJFAQSA-N 0.000 description 1
- BIZNDKMFQHDOIE-KKUMJFAQSA-N Leu-Phe-Asn Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=CC=C1 BIZNDKMFQHDOIE-KKUMJFAQSA-N 0.000 description 1
- KIZIOFNVSOSKJI-CIUDSAMLSA-N Leu-Ser-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N KIZIOFNVSOSKJI-CIUDSAMLSA-N 0.000 description 1
- RIHIGSWBLHSGLV-CQDKDKBSSA-N Leu-Tyr-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O RIHIGSWBLHSGLV-CQDKDKBSSA-N 0.000 description 1
- WUHBLPVELFTPQK-KKUMJFAQSA-N Leu-Tyr-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O WUHBLPVELFTPQK-KKUMJFAQSA-N 0.000 description 1
- RDFIVFHPOSOXMW-ACRUOGEOSA-N Leu-Tyr-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RDFIVFHPOSOXMW-ACRUOGEOSA-N 0.000 description 1
- MVJRBCJCRYGCKV-GVXVVHGQSA-N Leu-Val-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O MVJRBCJCRYGCKV-GVXVVHGQSA-N 0.000 description 1
- AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 description 1
- FDBTVENULFNTAL-XQQFMLRXSA-N Leu-Val-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N FDBTVENULFNTAL-XQQFMLRXSA-N 0.000 description 1
- GAOJCVKPIGHTGO-UWVGGRQHSA-N Lys-Arg-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O GAOJCVKPIGHTGO-UWVGGRQHSA-N 0.000 description 1
- NCTDKZKNBDZDOL-GARJFASQSA-N Lys-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)N)C(=O)O NCTDKZKNBDZDOL-GARJFASQSA-N 0.000 description 1
- QUCDKEKDPYISNX-HJGDQZAQSA-N Lys-Asn-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QUCDKEKDPYISNX-HJGDQZAQSA-N 0.000 description 1
- SVJRVFPSHPGWFF-DCAQKATOSA-N Lys-Cys-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SVJRVFPSHPGWFF-DCAQKATOSA-N 0.000 description 1
- LLSUNJYOSCOOEB-GUBZILKMSA-N Lys-Glu-Asp Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O LLSUNJYOSCOOEB-GUBZILKMSA-N 0.000 description 1
- GQZMPWBZQALKJO-UWVGGRQHSA-N Lys-Gly-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O GQZMPWBZQALKJO-UWVGGRQHSA-N 0.000 description 1
- UETQMSASAVBGJY-QWRGUYRKSA-N Lys-Gly-His Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CNC=N1 UETQMSASAVBGJY-QWRGUYRKSA-N 0.000 description 1
- YDDDRTIPNTWGIG-SRVKXCTJSA-N Lys-Lys-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O YDDDRTIPNTWGIG-SRVKXCTJSA-N 0.000 description 1
- MGKFCQFVPKOWOL-CIUDSAMLSA-N Lys-Ser-Asp Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N MGKFCQFVPKOWOL-CIUDSAMLSA-N 0.000 description 1
- ZUGVARDEGWMMLK-SRVKXCTJSA-N Lys-Ser-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN ZUGVARDEGWMMLK-SRVKXCTJSA-N 0.000 description 1
- 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 description 1
- CRGKLOXHKICQOL-GARJFASQSA-N Met-Gln-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N CRGKLOXHKICQOL-GARJFASQSA-N 0.000 description 1
- NLHSFJQUHGCWSD-PYJNHQTQSA-N Met-Ile-His Chemical compound N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CNC=N1)C(O)=O NLHSFJQUHGCWSD-PYJNHQTQSA-N 0.000 description 1
- RMLLCGYYVZKKRT-CIUDSAMLSA-N Met-Ser-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O RMLLCGYYVZKKRT-CIUDSAMLSA-N 0.000 description 1
- XZFYRXDAULDNFX-UHFFFAOYSA-N N-L-cysteinyl-L-phenylalanine Natural products SCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XZFYRXDAULDNFX-UHFFFAOYSA-N 0.000 description 1
- PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 description 1
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 1
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- BJEYSVHMGIJORT-NHCYSSNCSA-N Phe-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 BJEYSVHMGIJORT-NHCYSSNCSA-N 0.000 description 1
- MDHZEOMXGNBSIL-DLOVCJGASA-N Phe-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N MDHZEOMXGNBSIL-DLOVCJGASA-N 0.000 description 1
- DDYIRGBOZVKRFR-AVGNSLFASA-N Phe-Asp-Glu Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N DDYIRGBOZVKRFR-AVGNSLFASA-N 0.000 description 1
- AEEQKUDWJGOFQI-SRVKXCTJSA-N Phe-Cys-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)O)N AEEQKUDWJGOFQI-SRVKXCTJSA-N 0.000 description 1
- RVRRHFPCEOVRKQ-KKUMJFAQSA-N Phe-His-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CC(=O)N)C(=O)O)N RVRRHFPCEOVRKQ-KKUMJFAQSA-N 0.000 description 1
- VZFPYFRVHMSSNA-JURCDPSOSA-N Phe-Ile-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=CC=C1 VZFPYFRVHMSSNA-JURCDPSOSA-N 0.000 description 1
- KBVJZCVLQWCJQN-KKUMJFAQSA-N Phe-Leu-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O KBVJZCVLQWCJQN-KKUMJFAQSA-N 0.000 description 1
- SMFGCTXUBWEPKM-KBPBESRZSA-N Phe-Leu-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 SMFGCTXUBWEPKM-KBPBESRZSA-N 0.000 description 1
- WEDZFLRYSIDIRX-IHRRRGAJSA-N Phe-Ser-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=CC=C1 WEDZFLRYSIDIRX-IHRRRGAJSA-N 0.000 description 1
- IAOZOFPONWDXNT-IXOXFDKPSA-N Phe-Ser-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IAOZOFPONWDXNT-IXOXFDKPSA-N 0.000 description 1
- DZZCICYRSZASNF-FXQIFTODSA-N Pro-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 DZZCICYRSZASNF-FXQIFTODSA-N 0.000 description 1
- CQZNGNCAIXMAIQ-UBHSHLNASA-N Pro-Ala-Phe Chemical compound C[C@H](NC(=O)[C@@H]1CCCN1)C(=O)N[C@@H](Cc1ccccc1)C(O)=O CQZNGNCAIXMAIQ-UBHSHLNASA-N 0.000 description 1
- CGBYDGAJHSOGFQ-LPEHRKFASA-N Pro-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 CGBYDGAJHSOGFQ-LPEHRKFASA-N 0.000 description 1
- LCRSGSIRKLXZMZ-BPNCWPANSA-N Pro-Ala-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LCRSGSIRKLXZMZ-BPNCWPANSA-N 0.000 description 1
- SSSFPISOZOLQNP-GUBZILKMSA-N Pro-Arg-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O SSSFPISOZOLQNP-GUBZILKMSA-N 0.000 description 1
- TUYWCHPXKQTISF-LPEHRKFASA-N Pro-Cys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CS)C(=O)N2CCC[C@@H]2C(=O)O TUYWCHPXKQTISF-LPEHRKFASA-N 0.000 description 1
- MGDFPGCFVJFITQ-CIUDSAMLSA-N Pro-Glu-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O MGDFPGCFVJFITQ-CIUDSAMLSA-N 0.000 description 1
- FRKBNXCFJBPJOL-GUBZILKMSA-N Pro-Glu-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FRKBNXCFJBPJOL-GUBZILKMSA-N 0.000 description 1
- PTLOFJZJADCNCD-DCAQKATOSA-N Pro-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1 PTLOFJZJADCNCD-DCAQKATOSA-N 0.000 description 1
- DMKWYMWNEKIPFC-IUCAKERBSA-N Pro-Gly-Arg Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O DMKWYMWNEKIPFC-IUCAKERBSA-N 0.000 description 1
- HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-N 0.000 description 1
- HAEGAELAYWSUNC-WPRPVWTQSA-N Pro-Gly-Val Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HAEGAELAYWSUNC-WPRPVWTQSA-N 0.000 description 1
- CHYAYDLYYIJCKY-OSUNSFLBSA-N Pro-Thr-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O CHYAYDLYYIJCKY-OSUNSFLBSA-N 0.000 description 1
- DLZBBDSPTJBOOD-BPNCWPANSA-N Pro-Tyr-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O DLZBBDSPTJBOOD-BPNCWPANSA-N 0.000 description 1
- HBZBPFLJNDXRAY-FXQIFTODSA-N Ser-Ala-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O HBZBPFLJNDXRAY-FXQIFTODSA-N 0.000 description 1
- WDXYVIIVDIDOSX-DCAQKATOSA-N Ser-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CCCN=C(N)N WDXYVIIVDIDOSX-DCAQKATOSA-N 0.000 description 1
- OLIJLNWFEQEFDM-SRVKXCTJSA-N Ser-Asp-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OLIJLNWFEQEFDM-SRVKXCTJSA-N 0.000 description 1
- BLPYXIXXCFVIIF-FXQIFTODSA-N Ser-Cys-Arg Chemical compound C(C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N)CN=C(N)N BLPYXIXXCFVIIF-FXQIFTODSA-N 0.000 description 1
- BQWCDDAISCPDQV-XHNCKOQMSA-N Ser-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N)C(=O)O BQWCDDAISCPDQV-XHNCKOQMSA-N 0.000 description 1
- BRGQQXQKPUCUJQ-KBIXCLLPSA-N Ser-Glu-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BRGQQXQKPUCUJQ-KBIXCLLPSA-N 0.000 description 1
- SVWQEIRZHHNBIO-WHFBIAKZSA-N Ser-Gly-Cys Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CS)C(O)=O SVWQEIRZHHNBIO-WHFBIAKZSA-N 0.000 description 1
- YMTLKLXDFCSCNX-BYPYZUCNSA-N Ser-Gly-Gly Chemical compound OC[C@H](N)C(=O)NCC(=O)NCC(O)=O YMTLKLXDFCSCNX-BYPYZUCNSA-N 0.000 description 1
- RIAKPZVSNBBNRE-BJDJZHNGSA-N Ser-Ile-Leu Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O RIAKPZVSNBBNRE-BJDJZHNGSA-N 0.000 description 1
- QYSFWUIXDFJUDW-DCAQKATOSA-N Ser-Leu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYSFWUIXDFJUDW-DCAQKATOSA-N 0.000 description 1
- UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 description 1
- JLPMFVAIQHCBDC-CIUDSAMLSA-N Ser-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N JLPMFVAIQHCBDC-CIUDSAMLSA-N 0.000 description 1
- IFLVBVIYADZIQO-DCAQKATOSA-N Ser-Met-Lys Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N IFLVBVIYADZIQO-DCAQKATOSA-N 0.000 description 1
- RRVFEDGUXSYWOW-BZSNNMDCSA-N Ser-Phe-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RRVFEDGUXSYWOW-BZSNNMDCSA-N 0.000 description 1
- ADJDNJCSPNFFPI-FXQIFTODSA-N Ser-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO ADJDNJCSPNFFPI-FXQIFTODSA-N 0.000 description 1
- JLKWJWPDXPKKHI-FXQIFTODSA-N Ser-Pro-Asn Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CC(=O)N)C(=O)O JLKWJWPDXPKKHI-FXQIFTODSA-N 0.000 description 1
- XGQKSRGHEZNWIS-IHRRRGAJSA-N Ser-Pro-Tyr Chemical compound N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O XGQKSRGHEZNWIS-IHRRRGAJSA-N 0.000 description 1
- JCLAFVNDBJMLBC-JBDRJPRFSA-N Ser-Ser-Ile Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JCLAFVNDBJMLBC-JBDRJPRFSA-N 0.000 description 1
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 1
- ILZAUMFXKSIUEF-SRVKXCTJSA-N Ser-Ser-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ILZAUMFXKSIUEF-SRVKXCTJSA-N 0.000 description 1
- XJDMUQCLVSCRSJ-VZFHVOOUSA-N Ser-Thr-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O XJDMUQCLVSCRSJ-VZFHVOOUSA-N 0.000 description 1
- RXUOAOOZIWABBW-XGEHTFHBSA-N Ser-Thr-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RXUOAOOZIWABBW-XGEHTFHBSA-N 0.000 description 1
- ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 1
- SDFUZKIAHWRUCS-QEJZJMRPSA-N Ser-Trp-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CO)N SDFUZKIAHWRUCS-QEJZJMRPSA-N 0.000 description 1
- TWLMXDWFVNEFFK-FJXKBIBVSA-N Thr-Arg-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O TWLMXDWFVNEFFK-FJXKBIBVSA-N 0.000 description 1
- TZKPNGDGUVREEB-FOHZUACHSA-N Thr-Asn-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O TZKPNGDGUVREEB-FOHZUACHSA-N 0.000 description 1
- LYGKYFKSZTUXGZ-ZDLURKLDSA-N Thr-Cys-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)NCC(O)=O LYGKYFKSZTUXGZ-ZDLURKLDSA-N 0.000 description 1
- XOTBWOCSLMBGMF-SUSMZKCASA-N Thr-Glu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOTBWOCSLMBGMF-SUSMZKCASA-N 0.000 description 1
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 1
- XUGYQLFEJYZOKQ-NGTWOADLSA-N Thr-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H]([C@@H](C)O)N XUGYQLFEJYZOKQ-NGTWOADLSA-N 0.000 description 1
- ZSPQUTWLWGWTPS-HJGDQZAQSA-N Thr-Lys-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZSPQUTWLWGWTPS-HJGDQZAQSA-N 0.000 description 1
- WTMPKZWHRCMMMT-KZVJFYERSA-N Thr-Pro-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WTMPKZWHRCMMMT-KZVJFYERSA-N 0.000 description 1
- MUAFDCVOHYAFNG-RCWTZXSCSA-N Thr-Pro-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MUAFDCVOHYAFNG-RCWTZXSCSA-N 0.000 description 1
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 1
- BZTSQFWJNJYZSX-JRQIVUDYSA-N Thr-Tyr-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O BZTSQFWJNJYZSX-JRQIVUDYSA-N 0.000 description 1
- QGVBFDIREUUSHX-IFFSRLJSSA-N Thr-Val-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O QGVBFDIREUUSHX-IFFSRLJSSA-N 0.000 description 1
- ILUOMMDDGREELW-OSUNSFLBSA-N Thr-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)[C@@H](C)O ILUOMMDDGREELW-OSUNSFLBSA-N 0.000 description 1
- MNYNCKZAEIAONY-XGEHTFHBSA-N Thr-Val-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O MNYNCKZAEIAONY-XGEHTFHBSA-N 0.000 description 1
- VZBWRZGNEPBRDE-HZUKXOBISA-N Trp-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N VZBWRZGNEPBRDE-HZUKXOBISA-N 0.000 description 1
- PTAWAMWPRFTACW-SZMVWBNQSA-N Trp-Gln-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N PTAWAMWPRFTACW-SZMVWBNQSA-N 0.000 description 1
- HRKOLWXWQSDMSK-XIRDDKMYSA-N Trp-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N HRKOLWXWQSDMSK-XIRDDKMYSA-N 0.000 description 1
- SVGAWGVHFIYAEE-JSGCOSHPSA-N Trp-Gly-Gln Chemical compound C1=CC=C2C(C[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)=CNC2=C1 SVGAWGVHFIYAEE-JSGCOSHPSA-N 0.000 description 1
- UIDJDMVRDUANDL-BVSLBCMMSA-N Trp-Tyr-Arg Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O UIDJDMVRDUANDL-BVSLBCMMSA-N 0.000 description 1
- BURPTJBFWIOHEY-UWJYBYFXSA-N Tyr-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BURPTJBFWIOHEY-UWJYBYFXSA-N 0.000 description 1
- OOEUVMFKKZYSRX-LEWSCRJBSA-N Tyr-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N OOEUVMFKKZYSRX-LEWSCRJBSA-N 0.000 description 1
- IIJWXEUNETVJPV-IHRRRGAJSA-N Tyr-Arg-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N)O IIJWXEUNETVJPV-IHRRRGAJSA-N 0.000 description 1
- PEVVXUGSAKEPEN-AVGNSLFASA-N Tyr-Asn-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PEVVXUGSAKEPEN-AVGNSLFASA-N 0.000 description 1
- XBWKCYFGRXKWGO-SRVKXCTJSA-N Tyr-Cys-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O XBWKCYFGRXKWGO-SRVKXCTJSA-N 0.000 description 1
- FQNUWOHNGJWNLM-QWRGUYRKSA-N Tyr-Cys-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)NCC(O)=O FQNUWOHNGJWNLM-QWRGUYRKSA-N 0.000 description 1
- FXYOYUMPUJONGW-FHWLQOOXSA-N Tyr-Gln-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 FXYOYUMPUJONGW-FHWLQOOXSA-N 0.000 description 1
- CKHQKYHIZCRTAP-SOUVJXGZSA-N Tyr-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)C(=O)O CKHQKYHIZCRTAP-SOUVJXGZSA-N 0.000 description 1
- GQVZBMROTPEPIF-SRVKXCTJSA-N Tyr-Ser-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GQVZBMROTPEPIF-SRVKXCTJSA-N 0.000 description 1
- VMRFIKXKOFNMHW-GUBZILKMSA-N Val-Arg-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N VMRFIKXKOFNMHW-GUBZILKMSA-N 0.000 description 1
- CFSSLXZJEMERJY-NRPADANISA-N Val-Gln-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O CFSSLXZJEMERJY-NRPADANISA-N 0.000 description 1
- CELJCNRXKZPTCX-XPUUQOCRSA-N Val-Gly-Ala Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O CELJCNRXKZPTCX-XPUUQOCRSA-N 0.000 description 1
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 1
- ILMVQSHENUZYIZ-JYJNAYRXSA-N Val-Met-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N ILMVQSHENUZYIZ-JYJNAYRXSA-N 0.000 description 1
- HJSLDXZAZGFPDK-ULQDDVLXSA-N Val-Phe-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C(C)C)N HJSLDXZAZGFPDK-ULQDDVLXSA-N 0.000 description 1
- QIVPZSWBBHRNBA-JYJNAYRXSA-N Val-Pro-Phe Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(O)=O QIVPZSWBBHRNBA-JYJNAYRXSA-N 0.000 description 1
- JXWGBRRVTRAZQA-ULQDDVLXSA-N Val-Tyr-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C(C)C)N JXWGBRRVTRAZQA-ULQDDVLXSA-N 0.000 description 1
- IECQJCJNPJVUSB-IHRRRGAJSA-N Val-Tyr-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(O)=O IECQJCJNPJVUSB-IHRRRGAJSA-N 0.000 description 1
- 108010039538 alanyl-glycyl-aspartyl-valine Proteins 0.000 description 1
- 108010069020 alanyl-prolyl-glycine Proteins 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 108010008355 arginyl-glutamine Proteins 0.000 description 1
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 1
- 108010029539 arginyl-prolyl-proline Proteins 0.000 description 1
- 108010093581 aspartyl-proline Proteins 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 108010069495 cysteinyltyrosine Proteins 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 1
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 108010087823 glycyltyrosine Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 108010090333 leucyl-lysyl-proline Proteins 0.000 description 1
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 108010073025 phenylalanylphenylalanine Proteins 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 1
- 108010070643 prolylglutamic acid Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 108010000998 wheylin-2 peptide Proteins 0.000 description 1
Images
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/463—Cellular immunotherapy characterised by recombinant expression
- A61K39/4631—Chimeric Antigen Receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/7056—Lectin superfamily, e.g. CD23, CD72
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明提供了一种新型嵌合受体组合物、重组载体、细胞及其应用。该新型嵌合受体组合物包括传统的嵌合抗原受体和包括NKG2D、DAP10和/或DAP12的全长序列或者截短片段的NKG2D嵌合受体,简称Dual CAR。本发明提供的嵌合受体组合物使常规CAR‑T细胞表达NKG2D胞外区及胞内信号区,扩大CAR‑T抗原识别谱,解决肿瘤异质性,在增强CAR‑T对表达目标靶抗原肿瘤细胞的杀伤能力的同时,实现了较低水平的因子释放,降低因子风暴发生的可能,增加CAR‑T安全性。
Description
技术领域
本发明涉及生物医药技术领域,具体涉及一种新型嵌合受体组合物、重组载体、细胞及其应用。
背景技术
传统肿瘤治疗的方法包括手术、放疗、化疗、靶向治疗等;近些年免疫疗法的发展为肿瘤治疗领域带来深刻的改变,尤其是以CTLA-4、PD-1/PD-L1通路抑制剂为代表的免疫检查点疗法和以CAR-T为代表的过继性细胞疗法。过继性细胞疗法包括TIL、NK、TCR-T、等。其中靶向CD19的CAR-T疗法在B细胞肿瘤中取得了优秀的临床疗效,并且在2017年有两款CAR-T产品被FDA批准用于B细胞白血病或者淋巴瘤的治疗。
虽然CAR-T在血液瘤中取得了重大进展,但在治疗血液瘤中细胞因子风暴等副作用发生率较高,大部分患者在接受CAR-T治疗过程中需要使用辅助手段降低细胞因子风暴带来的副作用。CAR-T在实体瘤治疗中效果差,其中一个重要原因为肿瘤异质性,CAR-T细胞杀伤实体瘤能力较弱并且无法完全清除肿瘤细胞,另外CAR-T在实体瘤治疗因子风暴发生率及因子风暴水平较血液瘤更高,副作用更严重,获益与临床风险比低影响了临床实体瘤患者对CAR-T治疗的接受度。
现有的解决方案一般采用双靶点等解决肿瘤异质性,在治疗过程中或提前介入,采用抗体对症治疗因子风暴或在CAR-T上设计安全开关,当因子风暴发生或CAR-T过度增殖时,使用抗体中和细胞因子或清除CAR-T细胞,降低CAR-T毒副作用。
NK细胞表面表达NKG2D,通过识别其配体如MICA或MICB等激活下游信号DAP10及DAP12等从而杀伤靶细胞,T细胞表面本身也表达NKG2D,胞内表达DAP10而不表达DAP12,正常情况下T细胞表面NKG2D识别其配体后无法有效激活胞内信号,从而不能杀伤靶细胞。本发明拟设计在常规CAR-T细胞表达NKG2D胞外区及胞内信号区,扩大CAR-T抗原识别谱的同时,解决肿瘤异质性。
发明内容
为了克服现有技术中的缺陷,本发明提供了一种新型嵌合受体组合物、重组载体、细胞及其应用,扩大CAR-T抗原识别谱的同时,解决肿瘤异质性,且降低因子风暴发生的可能,增加了CAR-T安全性。
为实现上述目的,本发明采用如下技术方案:
本发明的第一方面是提供一种新型嵌合受体组合物,其包括嵌合抗原受体和包括NKG2D、DAP10和/或DAP12的全长序列或者截短片段的NKG2D嵌合受体。
进一步地,该嵌合受体组合物包括嵌合抗原受体和NKG2D嵌合受体;该NKG2D嵌合受体包括NKG2D胞外区和DAP12胞内区序列。
进一步地,上述NKG2D嵌合受体还包括一个共刺激分子;该共刺激分子选自:CD28、4-1BB、DAP10、ICOS、OX40和CD40。
进一步地,上述嵌合抗原受体包括:胞外识别区、胞外铰链区、跨膜区和胞内信号区。
进一步地,上述胞外识别区包括识别肿瘤相关抗原或肿瘤特异性抗原的抗体或抗体片段。
进一步地,上述肿瘤相关抗原或肿瘤特异性抗原选自:CD19、BCMA、CD22、CD20、CD123、CD30、CD38、CD138、CD56、CD7、CLL-1、CD10、CD34、CS1、CD16、CD4、CD5、IL-1-RAP、ITGB7、k-IgG、TAC1、TRBC1、MUC1、NKG2D、PD-L1、CD133、CD177、LeY、CD70、ROR1、AFP、AXL、CD80、CD86、DLL3、DR5、FAP、LMP1、MAGE-A1、MAGE-A4、MG7、MUC16、PMEL、ROR2、VEGFR2、CD171、Claudin 18.2、Claudin 6、EphA2、ErbB、Fra、PSCA、cMet、IL13Ra2、EPCAM、EGFR、PSMA、EGFRvIII、GPC3、CEA、HER2、GD2和Mesothelin。
进一步地,上述铰链区的序列来源于CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80和IgG的至少一种,上述跨膜区的序列来源于CD2、CD27、LFA-1(CD11a/CD18)、CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80、CD3ζ和CD3ε的至少一种,上述胞内信号区的序列来源于Toll样受体、CD2、CD27、LFA-1(CD11a/CD18)、CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80、DAP10、DAP12、CD3ζ和CD3ε等中的至少一种。
进一步地,上述嵌合抗原受体的氨基酸序列为SEQ ID NO.1。
进一步地,上述嵌合受体组合物还包括连接肽,连接上述嵌合抗原受体和嵌合受体;该连接肽为自切割多肽2A肽;该2A肽包括F2A、P2A、T2A和E2A;优选为P2A,其氨基酸序列为SEQ ID NO.10。
进一步地,上述嵌合受体的氨基酸序列选自以下序列的一条:SEQ IDNO.2~SEQID NO.9;优选为SEQ ID NO.4或SEQ ID NO.7。
本发明的第二方面是提供编码上述嵌合受体组合物的核酸序列。
本发明的第三方面是提供包含上述核酸序列的载体。
本发明的第四方面是提供表达上述嵌合受体组合物、含有上述核酸序列或者上述载体的细胞。
进一步地,上述细胞选自以下细胞中的一种:T细胞、NK细胞、DC细胞和巨噬细胞。
进一步地,上述T细胞选自αβT细胞、γδT细胞或NKT细胞。
本发明的第五方面是提供一种治疗肿瘤的生物制剂,包括上述细胞作为主要活性成分。
本发明的第六方面是提供上述细胞的制备方法,包括将上述载体转染细胞的步骤。
本发明的第七方面是提供上述嵌合受体组合物、核酸序列、载体或细胞在制备抗肿瘤药物中的应用。
本发明采用以上技术方案,与现有技术相比,具有如下技术效果:
本发明提供的嵌合受体组合物使常规CAR-T细胞表达NKG2D胞外区及胞内信号区,扩大CAR-T抗原识别谱,解决肿瘤异质性,在增强CAR-T对表达目标靶抗原肿瘤细胞的杀伤能力的同时,实现了较低水平的因子释放,降低因子风暴发生的可能,增加CAR-T安全性。
附图说明
图1是本发明一实施例中序列名称为21007、21067-21074的嵌合受体组合物的结构示意图;
图2显示了本发明一实施例中构建的CAR-T细胞anti-CLDN18.2-CAR及NKG2D的表达结果;
图3显示了本发明一实施例中构建的细胞系293-CLDN18.2高表达CLDN18.2;
图4显示了本发明一实施例中293T表达较高水平的NKG2D配体MICA/B;
图5显示了本发明一实施例中Dual CAR-T细胞对细胞系293-CLDN18.2的杀伤效果;
图6显示了本发明一实施例中与细胞系293-CLDN18.2共孵育,CAR-T的增殖倍数;
图7显示了本发明一实施例中Dual CAR-T细胞对293T细胞的杀伤效果;
图8显示了本发明一实施例中Dual CAR-T细胞在杀伤的靶细胞293-CLDN18.2时有更低的因子分泌水平,其中图A-D分别显示了IL-2、IFN-γ、IL6和TNF-α的分泌水平;
图9显示了本发明一实施例中Dual CAR-T细胞在杀伤表达MICA/B的靶细胞时释放中等水平的细胞因子,其中图A-D分别显示了IFN-γ、TNF-α、IL6和IL-2的分泌水平。
具体实施方式
本发明构建了一种嵌合受体组合物,在传统的嵌合抗原受体表达载体基础上增加包括NKG2D、DAP10和/或DAP12的全长序列或者截短片段的NKG2D嵌合受体,将载体包装为慢病毒,将慢病毒转导细胞制备针对同时靶向CLDN18.2并表达NKG2D的免疫细胞,增加免疫细胞疗法的安全性。
本发明一实施例提供了一种新型嵌合受体组合物,其包括嵌合抗原受体和包括NKG2D、DAP10和/或DAP12的全长序列或者截短片段的NKG2D嵌合受体。
在本发明一优选的实施方式中,该嵌合受体组合物包括嵌合抗原受体和NKG2D嵌合受体;该NKG2D嵌合受体包括NKG2D胞外区和DAP12胞内区序列。
在本发明一优选的实施方式中,上述NKG2D嵌合受体还包括一个共刺激分子;该共刺激分子选自:CD28、4-1BB、DAP10、ICOS、OX40和CD40。
在本发明一优选的实施方式中,上述嵌合抗原受体包括:胞外识别区、胞外铰链区、跨膜区和胞内信号区。
在本发明一优选的实施方式中,上述胞外识别区包括识别肿瘤相关抗原或肿瘤特异性抗原的抗体或抗体片段。
在本发明一优选的实施方式中,上述肿瘤相关抗原或肿瘤特异性抗原选自但不限于:CD19、BCMA、CD22、CD20、CD123、CD30、CD38、CD138、CD56、CD7、CLL-1、CD10、CD34、CS1、CD16、CD4、CD5、IL-1-RAP、ITGB7、k-IgG、TAC1、TRBC1、MUC1、NKG2D、PD-L1、CD133、CD177、LeY、CD70、ROR1、AFP、AXL、CD80、CD86、DLL3、DR5、FAP、LMP1、MAGE-A1、MAGE-A4、MG7、MUC16、PMEL、ROR2、VEGFR2、CD171、Claudin 18.2、Claudin 6、EphA2、ErbB、Fra、PSCA、cMet、IL13Ra2、EPCAM、EGFR、PSMA、EGFRvIII、GPC3、CEA、HER2、GD2和Mesothelin。
在本发明一优选的实施方式中,上述铰链区的序列来源于CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80和IgG的至少一种,上述跨膜区的序列来源于CD2、CD27、LFA-1(CD11a/CD18)、CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80、CD3ζ和CD3ε的至少一种,上述胞内信号区的序列来源于Toll样受体、CD2、CD27、LFA-1(CD11a/CD18)、CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80、DAP10、DAP12、CD3ζ和CD3ε等中的至少一种。
在本发明一优选的实施方式中,上述嵌合抗原受体的氨基酸序列为SEQ ID NO.1。
在本发明一优选的实施方式中,上述嵌合受体组合物还包括连接肽,连接上述嵌合抗原受体和嵌合受体;该连接肽为自切割多肽2A肽;该2A肽包括F2A、P2A、T2A和E2A;优选为P2A,其氨基酸序列为SEQ ID NO.10。
在本发明一优选的实施方式中,上述嵌合受体的氨基酸序列选自以下序列的一条:SEQ ID NO.2~SEQ ID NO.9;优选为SEQ ID NO.4或SEQ ID NO.7。
本发明一实施例提供了编码上述嵌合受体组合物的核酸序列。
本发明一实施例提供了包含上述核酸序列的载体。
本发明一实施例提供了表达上述嵌合受体组合物、含有上述核酸序列或者上述载体的细胞。
在本发明一优选的实施方式中,上述细胞选自以下细胞中的一种:T细胞、NK细胞、DC细胞和巨噬细胞。
在本发明一优选的实施方式中,上述T细胞选自αβT细胞、γδT细胞或NKT细胞。
本发明一实施例提供了一种治疗肿瘤的生物制剂,包括上述细胞作为主要活性成分;优选地还包括药学上可接受载体、稀释剂或赋形剂。
本发明一实施例提供了上述细胞的制备方法,包括将上述载体转染细胞的步骤。
本发明一实施例提供了上述嵌合受体组合物、核酸序列、载体或细胞在制备抗肿瘤药物中的应用。
下面通过具体实施例和附图对本发明进行详细和具体的介绍,以使更好的理解本发明,但是下述实施例并不限制本发明范围。
实施例中方法如无特殊说明的采用常规方法,使用的试剂如无特殊说明的使用常规市售试剂或按常规方法配制的试剂。
实施例1
本实施例提供了一种新型嵌合受体组合物;该新型嵌合受体组合物(在下文中称为Dual CAR,其对应的CAR-T细胞称为Dual CAR-T)包括氨基酸序列为SEQ ID NO.1的anti-CLDN18.2-CAR(传统二代Claudin18.2 CAR分子,下文称为21007),以及如SEQ ID NO.2~9所示的嵌合受体序列(结构序列如图1所示),具体的氨基酸序列对应下表1中的序列名称为21067~21074的序列。
表1 anti-CLDN18.2-CAR以及嵌合受体组合物的序列信息
如图1所示,上述嵌合受体组合物除包括氨基酸序列如SEQ ID NO.1的嵌合抗原受体,还包括的序列信息如下:
(1)P2A,其氨基酸序列如下:
GSGATNFSLLKQAGDVEENPGP(SEQ ID NO.10);
(2)DAP12ICD(胞内区),其氨基酸序列如下:
YFLGRLVPRGRGAAEAATRKQRITETESPYQELQGQRSDVYSDLNTQRPYYK(SEQ ID NO.11);
(3)DAP10ICD,其氨基酸序列如下:
LCARPRRSPAQEDGKVYINMPGRG(SEQ ID NO.12);
(4)NKG2DFL(全长序列),其氨基酸序列如下:
MGWIRGRRSRHSWEMSEFHNYNLDLKKSDFSTRWQKQRCPVVKSKCRENASPFFFCCFIAVAMGIRFIIMVTIWSAVFLNSLFNQEVQIPLTESYCGPCPKNWICYKNNCYQFFDESKNWYESQASCMSQNASLLKVYSKEDQDLLKLVKSYHWMGLVHIPTNGSWQWEDGSILSPNLLTIIEMQKGDCALYASSFKGYIENCSTPNTYICMQRTV(SEQID NO.13);
(5)CD8 hinge(铰链区),其氨基酸序列如下:
TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD(SEQ ID NO.14);
(6)CD8 TM(跨膜区),其氨基酸序列如下:
IYIWAPLAGTCGVLLLSLVITLYC(SEQ ID NO.15);
(7)DAP10FL,其氨基酸序列如下:
MIHLGHILFLLLLPVAAAQTTPGERSSLPAFYPGTSGSCSGCGSLSLPLLAGLVAADAVASLLIVGAVFLCARPRRSPAQEDGKVYINMPGRG(SEQ ID NO.16);
(8)DAP12FL,其氨基酸序列如下:
MGGLEPCSRLLLLPLLLAVSGLRPVQAQAQSDCSCSTVSPGVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAAEAATRKQRITETESPYQELQGQRSDVYSDLNTQRP YYK(SEQ ID NO.17);
(9)DAP12ECD+TM(胞外区及跨膜区),其氨基酸序列如下:
LRPVQAQAQSDCSCSTVSPGVLAGIVMGDLVLTVLIALAV(SEQ ID NO.18);
(10)T2A,其氨基酸序列如下:
GSGEGRGSLLTCGDVEENPGP(SEQ ID NO.19)。
实施例2
本实施例提供表达上述嵌合受体的Dual CAR-T细胞,其构建方法包括如下步骤:
1.表达载体构建:Dual CAR分子和慢病毒载体骨架部分分别由CRO公司使用全基因合成技术构建得到。通过常规分子克隆手段,将Dual CAR片段克隆至慢病毒载体,所构建的质粒名称如上表1所示。各质粒通过对插入片段全序列测通验证证明构建成功。
2.慢病毒包装和滴度测定
第一天:
1)在T75培养瓶中接种293T细胞,数量为5×106,培养体积为20ml;
第二天:
2)包病毒前确认293T细胞汇合度在70%-80%左右,并进行等体积换液;
3)转染复合物的配制和转染:
分别配置Tube A和Tube B,体系如下所示,并进行颠倒或者低速振荡混匀;
Tube A:Opti-MEM(2ml)+Lipo3000(55μl);
Tube B:Opti-MEM(2ml)+P3000(46μl)+辅助质粒18μg+Dual CAR主质粒6μg;
将Tube A加入到Tube B中,振荡混匀,室温孵育15分钟;
将第3步中换过液的培养瓶翻面,使培养基处于培养瓶另一面,将Tube A+B混合物加入,轻摇混匀后,再将培养瓶缓慢翻回正面,后继续培养48h;
第四天:
4)转染完成培养2天后,收集上清,500g离心10min,用0.45μm滤器过滤上清至50ml离心管中,包好封口膜,10000g,4℃离心过夜,可见白色病毒沉淀;弃上清后倒置离心管至上清流尽后用200μl AIM-V培养基溶解沉淀后,取2μl按照后续步骤测定滴度,其余置于-80℃保存。
5)将2μl重悬病毒上清加至198μl 1640培养基中稀释病毒,后在24孔板中按照每孔2×105数量Jurkat T细胞分别加入稀释后的病毒2μl、10μl和50μl一共3个孔,并加入终浓度为5μg/ml的Polybrene辅助病毒感染。
第六天:
6)使用Anti-VHH-FITC抗体检测病毒滴度,滴度在2.5×107-1.2×108之间,可满足常规体外CAR-T构建实验要求。
3.CAR-T的检测
将上述包装的慢病毒感染T细胞,检测T细胞上anti-CLDN18.2-CAR及NKG2D的表达,结果如图2所示。
由图2可知,anti-CLDN18.2-CAR-T细胞有较低水平的NKG2D表达,Dual CAR-T细胞相比anti-CLDN18.2-CAR-T细胞有较高的NKG2D表达水平,同时正常表达anti-CLDN18.2-CAR。说明NKG2D嵌合受体在Dual CAR-T细胞表面成功表达。
实施例3
本实施例验证Dual CAR-T细胞对靶细胞的杀伤效果,具体的步骤和结果如下:
(1)293细胞基础上构建了过表达CLDN18.2抗原的细胞系293-CLDN18.2,该细胞系高表达CLDN18.2(如图3)。
(2)检测细胞系NKG2D配体MICA/B的表达:鉴定了239T细胞系上MICA/B的表达水平,293T细胞系表达较高水平的MICA/B(如图4)。
(3)CAR-T细胞与293-CLDN18.2按2:1及0.5:1的效靶比混合,孵育5h,Annexin V流式检测CAR-T对靶细胞杀伤效果,anti-CLDN18.2-CAR-T及Dual CAR-T相对unT(未转导的T)细胞,对293-CLDN18.2有较强的杀伤效果,其中21069及21072在2:1效靶比时有相对传统CAR-T(21007)更强的杀伤效果(如图5)。此外,将293-CLDN18.2与CAR-T共孵育,21069及21072Dual CAR-T增殖倍数明显高于传统的CAR-T细胞(21007)(如图6)。
CAR-T细胞与293T细胞按2:1及0.5:1的效靶比混合,孵育5h,Annexin V流式检测CAR-T对靶细胞杀伤效果,anti-CLDN18.2-CAR-T及Dual CAR-T相对unT(未转导的T)细胞,对表达MICA/B的靶细胞有较强的杀伤效果,其中21069及21072在2:1效靶比时有相对传统CAR-T更强的杀伤效果(如图7)。
实施例4
本实施例验证Dual CAR-T细胞在杀伤的靶细胞293-CLDN18.2时有更低的因子分泌水平,具体的步骤和结果如下:
采用实施例3构建的细胞系293-CLDN18.2;将CAR-T细胞与293-CLDN18.2按2:1的效靶比混合,孵育24h,流式检测CAR-T细胞因子释放,使用Biolegend的多因子检测试剂盒,取15μl/样品的效应细胞与靶细胞孵育的上清至新的V型96孔板中,加入混合稀释后的磁珠15μl/样品及15μl/样品的assay buffer,封板膜密封,500rpm室温震荡2h,250g离心5min,去上清,加入200μl/样品的wash buffer,250g离心5min,去上清,加入15μl/样品的检测抗体,500rpm室温震荡1h,加入15μl/样品的SA-PE,500rpm室温震荡30min,250g离心5min,去上清,加入200μl/样品的wash buffer,250g离心5min,去上清,加入150μl/样品的WashBuffer,上机检测。结果显示anti-CLDN18.2-CAR-T及Dual CAR-T细胞在杀伤293-CLDN18.2靶细胞时,21067、21068、21069、21070、21072等Dual CAR-T有明显更低的IFN-γ、IL2、IL6和TNF-α分泌水平(如图8)。
实施例5
本实施例验证Dual CAR-T细胞在杀伤表达MICA/B的靶细胞时释放中等水平的细胞因子,具体的步骤和结果如下:
将CAR-T细胞与293T按2:1的效靶比混合,孵育24h,流式检测CAR-T细胞因子释放,anti-CLDN18.2-CAR-T细胞及Dual CAR-T细胞在杀伤293T靶细胞时,21068、21069、21070、21072等Dual CAR-T有中等水平的IFN-γ分泌水平,较低的TNF-α、IL2及IL6分泌水平(如图9)。
以上对本发明的具体实施例进行了详细描述,但其只作为范例,本发明并不限制于以上描述的具体实施例。对于本领域技术人员而言,任何对本发明进行等同修改和替代也都在本发明的范畴之中。因此,在不脱离本发明精神和范围下所作的均等变换和修改,都应涵盖在本发明的范围内。
序列表
<110> 上海易慕峰生物科技有限公司
<120> 一种新型嵌合受体组合物、重组载体、细胞及其应用
<160> 19
<170> SIPOSequenceListing 1.0
<210> 1
<211> 361
<212> PRT
<213> Artificial Sequence
<400> 1
Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro
1 5 10 15
Ala Phe Leu Leu Ile Pro Glu Val Gln Leu Val Glu Ser Gly Gly Gly
20 25 30
Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
35 40 45
Ser Phe Phe Arg Ile Val Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly
50 55 60
Lys Gly Arg Glu Leu Val Ala Thr Ile Thr Arg Gly Gly Ser Thr Tyr
65 70 75 80
Tyr Ala Asp Ser Met Lys Gly Arg Ser Thr Ile Ser Arg Asp Asn Ala
85 90 95
Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr
100 105 110
Ala Val Tyr Tyr Cys Asn Val Arg Val Glu Val Pro Phe Met Gln Pro
115 120 125
Asn Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ile Glu
130 135 140
Val Met Tyr Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn Gly Thr
145 150 155 160
Ile Ile His Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro
165 170 175
Gly Pro Ser Lys Pro Phe Trp Val Leu Val Val Val Gly Gly Val Leu
180 185 190
Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val
195 200 205
Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr
210 215 220
Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro
225 230 235 240
Pro Arg Asp Phe Ala Ala Tyr Arg Ser Arg Val Lys Phe Ser Arg Ser
245 250 255
Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu
260 265 270
Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg
275 280 285
Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln
290 295 300
Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr
305 310 315 320
Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp
325 330 335
Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala
340 345 350
Leu His Met Gln Ala Leu Pro Pro Arg
355 360
<210> 2
<211> 292
<212> PRT
<213> Artificial Sequence
<400> 2
Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala
1 5 10 15
Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu
20 25 30
Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg
35 40 45
Pro Tyr Tyr Lys Leu Cys Ala Arg Pro Arg Arg Ser Pro Ala Gln Glu
50 55 60
Asp Gly Lys Val Tyr Ile Asn Met Pro Gly Arg Gly Met Gly Trp Ile
65 70 75 80
Arg Gly Arg Arg Ser Arg His Ser Trp Glu Met Ser Glu Phe His Asn
85 90 95
Tyr Asn Leu Asp Leu Lys Lys Ser Asp Phe Ser Thr Arg Trp Gln Lys
100 105 110
Gln Arg Cys Pro Val Val Lys Ser Lys Cys Arg Glu Asn Ala Ser Pro
115 120 125
Phe Phe Phe Cys Cys Phe Ile Ala Val Ala Met Gly Ile Arg Phe Ile
130 135 140
Ile Met Val Thr Ile Trp Ser Ala Val Phe Leu Asn Ser Leu Phe Asn
145 150 155 160
Gln Glu Val Gln Ile Pro Leu Thr Glu Ser Tyr Cys Gly Pro Cys Pro
165 170 175
Lys Asn Trp Ile Cys Tyr Lys Asn Asn Cys Tyr Gln Phe Phe Asp Glu
180 185 190
Ser Lys Asn Trp Tyr Glu Ser Gln Ala Ser Cys Met Ser Gln Asn Ala
195 200 205
Ser Leu Leu Lys Val Tyr Ser Lys Glu Asp Gln Asp Leu Leu Lys Leu
210 215 220
Val Lys Ser Tyr His Trp Met Gly Leu Val His Ile Pro Thr Asn Gly
225 230 235 240
Ser Trp Gln Trp Glu Asp Gly Ser Ile Leu Ser Pro Asn Leu Leu Thr
245 250 255
Ile Ile Glu Met Gln Lys Gly Asp Cys Ala Leu Tyr Ala Ser Ser Phe
260 265 270
Lys Gly Tyr Ile Glu Asn Cys Ser Thr Pro Asn Thr Tyr Ile Cys Met
275 280 285
Gln Arg Thr Val
290
<210> 3
<211> 241
<212> PRT
<213> Artificial Sequence
<400> 3
Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala
1 5 10 15
Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu
20 25 30
Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg
35 40 45
Pro Tyr Tyr Lys Leu Cys Ala Arg Pro Arg Arg Ser Pro Ala Gln Glu
50 55 60
Asp Gly Lys Val Tyr Ile Asn Met Pro Gly Arg Gly Pro Phe Phe Phe
65 70 75 80
Cys Cys Phe Ile Ala Val Ala Met Gly Ile Arg Phe Ile Ile Met Val
85 90 95
Thr Ile Trp Ser Ala Val Phe Leu Asn Ser Leu Phe Asn Gln Glu Val
100 105 110
Gln Ile Pro Leu Thr Glu Ser Tyr Cys Gly Pro Cys Pro Lys Asn Trp
115 120 125
Ile Cys Tyr Lys Asn Asn Cys Tyr Gln Phe Phe Asp Glu Ser Lys Asn
130 135 140
Trp Tyr Glu Ser Gln Ala Ser Cys Met Ser Gln Asn Ala Ser Leu Leu
145 150 155 160
Lys Val Tyr Ser Lys Glu Asp Gln Asp Leu Leu Lys Leu Val Lys Ser
165 170 175
Tyr His Trp Met Gly Leu Val His Ile Pro Thr Asn Gly Ser Trp Gln
180 185 190
Trp Glu Asp Gly Ser Ile Leu Ser Pro Asn Leu Leu Thr Ile Ile Glu
195 200 205
Met Gln Lys Gly Asp Cys Ala Leu Tyr Ala Ser Ser Phe Lys Gly Tyr
210 215 220
Ile Glu Asn Cys Ser Thr Pro Asn Thr Tyr Ile Cys Met Gln Arg Thr
225 230 235 240
Val
<210> 4
<211> 279
<212> PRT
<213> Artificial Sequence
<400> 4
Met Ile His Leu Gly His Ile Leu Phe Leu Leu Leu Leu Pro Val Ala
1 5 10 15
Ala Ala Phe Asn Gln Glu Val Gln Ile Pro Leu Thr Glu Ser Tyr Cys
20 25 30
Gly Pro Cys Pro Lys Asn Trp Ile Cys Tyr Lys Asn Asn Cys Tyr Gln
35 40 45
Phe Phe Asp Glu Ser Lys Asn Trp Tyr Glu Ser Gln Ala Ser Cys Met
50 55 60
Ser Gln Asn Ala Ser Leu Leu Lys Val Tyr Ser Lys Glu Asp Gln Asp
65 70 75 80
Leu Leu Lys Leu Val Lys Ser Tyr His Trp Met Gly Leu Val His Ile
85 90 95
Pro Thr Asn Gly Ser Trp Gln Trp Glu Asp Gly Ser Ile Leu Ser Pro
100 105 110
Asn Leu Leu Thr Ile Ile Glu Met Gln Lys Gly Asp Cys Ala Leu Tyr
115 120 125
Ala Ser Ser Phe Lys Gly Tyr Ile Glu Asn Cys Ser Thr Pro Asn Thr
130 135 140
Tyr Ile Cys Met Gln Arg Thr Val Gln Thr Thr Pro Gly Glu Arg Ser
145 150 155 160
Ser Leu Pro Ala Phe Tyr Pro Gly Thr Ser Gly Ser Cys Ser Gly Cys
165 170 175
Gly Ser Leu Ser Leu Pro Leu Leu Ala Gly Leu Val Ala Ala Asp Ala
180 185 190
Val Ala Ser Leu Leu Ile Val Gly Ala Val Phe Leu Cys Ala Arg Pro
195 200 205
Arg Arg Ser Pro Ala Gln Glu Asp Gly Lys Val Tyr Ile Asn Met Pro
210 215 220
Gly Arg Gly Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala
225 230 235 240
Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro
245 250 255
Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn
260 265 270
Thr Gln Arg Pro Tyr Tyr Lys
275
<210> 5
<211> 300
<212> PRT
<213> Artificial Sequence
<400> 5
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Phe Asn Gln Glu Val Gln Ile Pro Leu Thr Glu
20 25 30
Ser Tyr Cys Gly Pro Cys Pro Lys Asn Trp Ile Cys Tyr Lys Asn Asn
35 40 45
Cys Tyr Gln Phe Phe Asp Glu Ser Lys Asn Trp Tyr Glu Ser Gln Ala
50 55 60
Ser Cys Met Ser Gln Asn Ala Ser Leu Leu Lys Val Tyr Ser Lys Glu
65 70 75 80
Asp Gln Asp Leu Leu Lys Leu Val Lys Ser Tyr His Trp Met Gly Leu
85 90 95
Val His Ile Pro Thr Asn Gly Ser Trp Gln Trp Glu Asp Gly Ser Ile
100 105 110
Leu Ser Pro Asn Leu Leu Thr Ile Ile Glu Met Gln Lys Gly Asp Cys
115 120 125
Ala Leu Tyr Ala Ser Ser Phe Lys Gly Tyr Ile Glu Asn Cys Ser Thr
130 135 140
Pro Asn Thr Tyr Ile Cys Met Gln Arg Thr Val Thr Thr Thr Pro Ala
145 150 155 160
Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser
165 170 175
Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr
180 185 190
Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala
195 200 205
Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys
210 215 220
Leu Cys Ala Arg Pro Arg Arg Ser Pro Ala Gln Glu Asp Gly Lys Val
225 230 235 240
Tyr Ile Asn Met Pro Gly Arg Gly Tyr Phe Leu Gly Arg Leu Val Pro
245 250 255
Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr
260 265 270
Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val
275 280 285
Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys
290 295 300
<210> 6
<211> 318
<212> PRT
<213> Artificial Sequence
<400> 6
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Phe Asn Gln Glu Val Gln Ile Pro Leu Thr Glu
20 25 30
Ser Tyr Cys Gly Pro Cys Pro Lys Asn Trp Ile Cys Tyr Lys Asn Asn
35 40 45
Cys Tyr Gln Phe Phe Asp Glu Ser Lys Asn Trp Tyr Glu Ser Gln Ala
50 55 60
Ser Cys Met Ser Gln Asn Ala Ser Leu Leu Lys Val Tyr Ser Lys Glu
65 70 75 80
Asp Gln Asp Leu Leu Lys Leu Val Lys Ser Tyr His Trp Met Gly Leu
85 90 95
Val His Ile Pro Thr Asn Gly Ser Trp Gln Trp Glu Asp Gly Ser Ile
100 105 110
Leu Ser Pro Asn Leu Leu Thr Ile Ile Glu Met Gln Lys Gly Asp Cys
115 120 125
Ala Leu Tyr Ala Ser Ser Phe Lys Gly Tyr Ile Glu Asn Cys Ser Thr
130 135 140
Pro Asn Thr Tyr Ile Cys Met Gln Arg Thr Val Thr Thr Thr Pro Ala
145 150 155 160
Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala Ser Gln Pro Leu Ser
165 170 175
Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly Gly Ala Val His Thr
180 185 190
Arg Gly Leu Asp Phe Ala Cys Asp Ile Tyr Ile Trp Ala Pro Leu Ala
195 200 205
Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val Ile Thr Leu Tyr Cys
210 215 220
Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met
225 230 235 240
Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe
245 250 255
Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Tyr Phe Leu Gly Arg Leu
260 265 270
Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg
275 280 285
Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser
290 295 300
Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys
305 310 315
<210> 7
<211> 314
<212> PRT
<213> Artificial Sequence
<400> 7
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Phe Asn Gln Glu Val Gln Ile Pro Leu Thr Glu
20 25 30
Ser Tyr Cys Gly Pro Cys Pro Lys Asn Trp Ile Cys Tyr Lys Asn Asn
35 40 45
Cys Tyr Gln Phe Phe Asp Glu Ser Lys Asn Trp Tyr Glu Ser Gln Ala
50 55 60
Ser Cys Met Ser Gln Asn Ala Ser Leu Leu Lys Val Tyr Ser Lys Glu
65 70 75 80
Asp Gln Asp Leu Leu Lys Leu Val Lys Ser Tyr His Trp Met Gly Leu
85 90 95
Val His Ile Pro Thr Asn Gly Ser Trp Gln Trp Glu Asp Gly Ser Ile
100 105 110
Leu Ser Pro Asn Leu Leu Thr Ile Ile Glu Met Gln Lys Gly Asp Cys
115 120 125
Ala Leu Tyr Ala Ser Ser Phe Lys Gly Tyr Ile Glu Asn Cys Ser Thr
130 135 140
Pro Asn Thr Tyr Ile Cys Met Gln Arg Thr Val Ile Glu Val Met Tyr
145 150 155 160
Pro Pro Pro Tyr Leu Asp Asn Glu Lys Ser Asn Gly Thr Ile Ile His
165 170 175
Val Lys Gly Lys His Leu Cys Pro Ser Pro Leu Phe Pro Gly Pro Ser
180 185 190
Lys Pro Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr
195 200 205
Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Arg Ser Lys
210 215 220
Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro Arg Arg
225 230 235 240
Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro Arg Asp
245 250 255
Phe Ala Ala Tyr Arg Ser Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly
260 265 270
Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr
275 280 285
Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser
290 295 300
Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys
305 310
<210> 8
<211> 113
<212> PRT
<213> Artificial Sequence
<400> 8
Met Gly Gly Leu Glu Pro Cys Ser Arg Leu Leu Leu Leu Pro Leu Leu
1 5 10 15
Leu Ala Val Ser Gly Leu Arg Pro Val Gln Ala Gln Ala Gln Ser Asp
20 25 30
Cys Ser Cys Ser Thr Val Ser Pro Gly Val Leu Ala Gly Ile Val Met
35 40 45
Gly Asp Leu Val Leu Thr Val Leu Ile Ala Leu Ala Val Tyr Phe Leu
50 55 60
Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg
65 70 75 80
Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly
85 90 95
Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr
100 105 110
Lys
<210> 9
<211> 486
<212> PRT
<213> Artificial Sequence
<400> 9
Met Ala Leu Pro Val Thr Ala Leu Leu Leu Pro Leu Ala Leu Leu Leu
1 5 10 15
His Ala Ala Arg Pro Met Gly Trp Ile Arg Gly Arg Arg Ser Arg His
20 25 30
Ser Trp Glu Met Ser Glu Phe His Asn Tyr Asn Leu Asp Leu Lys Lys
35 40 45
Ser Asp Phe Ser Thr Arg Trp Gln Lys Gln Arg Cys Pro Val Val Lys
50 55 60
Ser Lys Cys Arg Glu Asn Ala Ser Pro Phe Phe Phe Cys Cys Phe Ile
65 70 75 80
Ala Val Ala Met Gly Ile Arg Phe Ile Ile Met Val Thr Ile Trp Ser
85 90 95
Ala Val Phe Leu Asn Ser Leu Phe Asn Gln Glu Val Gln Ile Pro Leu
100 105 110
Thr Glu Ser Tyr Cys Gly Pro Cys Pro Lys Asn Trp Ile Cys Tyr Lys
115 120 125
Asn Asn Cys Tyr Gln Phe Phe Asp Glu Ser Lys Asn Trp Tyr Glu Ser
130 135 140
Gln Ala Ser Cys Met Ser Gln Asn Ala Ser Leu Leu Lys Val Tyr Ser
145 150 155 160
Lys Glu Asp Gln Asp Leu Leu Lys Leu Val Lys Ser Tyr His Trp Met
165 170 175
Gly Leu Val His Ile Pro Thr Asn Gly Ser Trp Gln Trp Glu Asp Gly
180 185 190
Ser Ile Leu Ser Pro Asn Leu Leu Thr Ile Ile Glu Met Gln Lys Gly
195 200 205
Asp Cys Ala Leu Tyr Ala Ser Ser Phe Lys Gly Tyr Ile Glu Asn Cys
210 215 220
Ser Thr Pro Asn Thr Tyr Ile Cys Met Gln Arg Thr Val Gly Ser Gly
225 230 235 240
Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro
245 250 255
Gly Pro Met Gly Gly Leu Glu Pro Cys Ser Arg Leu Leu Leu Leu Pro
260 265 270
Leu Leu Leu Ala Val Ser Gly Leu Arg Pro Val Gln Ala Gln Ala Gln
275 280 285
Ser Asp Cys Ser Cys Ser Thr Val Ser Pro Gly Val Leu Ala Gly Ile
290 295 300
Val Met Gly Asp Leu Val Leu Thr Val Leu Ile Ala Leu Ala Val Tyr
305 310 315 320
Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala
325 330 335
Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu
340 345 350
Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro
355 360 365
Tyr Tyr Lys Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala
370 375 380
Gly Asp Val Glu Glu Asn Pro Gly Pro Met Ile His Leu Gly His Ile
385 390 395 400
Leu Phe Leu Leu Leu Leu Pro Val Ala Ala Ala Gln Thr Thr Pro Gly
405 410 415
Glu Arg Ser Ser Leu Pro Ala Phe Tyr Pro Gly Thr Ser Gly Ser Cys
420 425 430
Ser Gly Cys Gly Ser Leu Ser Leu Pro Leu Leu Ala Gly Leu Val Ala
435 440 445
Ala Asp Ala Val Ala Ser Leu Leu Ile Val Gly Ala Val Phe Leu Cys
450 455 460
Ala Arg Pro Arg Arg Ser Pro Ala Gln Glu Asp Gly Lys Val Tyr Ile
465 470 475 480
Asn Met Pro Gly Arg Gly
485
<210> 10
<211> 22
<212> PRT
<213> Artificial Sequence
<400> 10
Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val
1 5 10 15
Glu Glu Asn Pro Gly Pro
20
<210> 11
<211> 52
<212> PRT
<213> Artificial Sequence
<400> 11
Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala
1 5 10 15
Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu
20 25 30
Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg
35 40 45
Pro Tyr Tyr Lys
50
<210> 12
<211> 24
<212> PRT
<213> Artificial Sequence
<400> 12
Leu Cys Ala Arg Pro Arg Arg Ser Pro Ala Gln Glu Asp Gly Lys Val
1 5 10 15
Tyr Ile Asn Met Pro Gly Arg Gly
20
<210> 13
<211> 216
<212> PRT
<213> Artificial Sequence
<400> 13
Met Gly Trp Ile Arg Gly Arg Arg Ser Arg His Ser Trp Glu Met Ser
1 5 10 15
Glu Phe His Asn Tyr Asn Leu Asp Leu Lys Lys Ser Asp Phe Ser Thr
20 25 30
Arg Trp Gln Lys Gln Arg Cys Pro Val Val Lys Ser Lys Cys Arg Glu
35 40 45
Asn Ala Ser Pro Phe Phe Phe Cys Cys Phe Ile Ala Val Ala Met Gly
50 55 60
Ile Arg Phe Ile Ile Met Val Thr Ile Trp Ser Ala Val Phe Leu Asn
65 70 75 80
Ser Leu Phe Asn Gln Glu Val Gln Ile Pro Leu Thr Glu Ser Tyr Cys
85 90 95
Gly Pro Cys Pro Lys Asn Trp Ile Cys Tyr Lys Asn Asn Cys Tyr Gln
100 105 110
Phe Phe Asp Glu Ser Lys Asn Trp Tyr Glu Ser Gln Ala Ser Cys Met
115 120 125
Ser Gln Asn Ala Ser Leu Leu Lys Val Tyr Ser Lys Glu Asp Gln Asp
130 135 140
Leu Leu Lys Leu Val Lys Ser Tyr His Trp Met Gly Leu Val His Ile
145 150 155 160
Pro Thr Asn Gly Ser Trp Gln Trp Glu Asp Gly Ser Ile Leu Ser Pro
165 170 175
Asn Leu Leu Thr Ile Ile Glu Met Gln Lys Gly Asp Cys Ala Leu Tyr
180 185 190
Ala Ser Ser Phe Lys Gly Tyr Ile Glu Asn Cys Ser Thr Pro Asn Thr
195 200 205
Tyr Ile Cys Met Gln Arg Thr Val
210 215
<210> 14
<211> 45
<212> PRT
<213> Artificial Sequence
<400> 14
Thr Thr Thr Pro Ala Pro Arg Pro Pro Thr Pro Ala Pro Thr Ile Ala
1 5 10 15
Ser Gln Pro Leu Ser Leu Arg Pro Glu Ala Cys Arg Pro Ala Ala Gly
20 25 30
Gly Ala Val His Thr Arg Gly Leu Asp Phe Ala Cys Asp
35 40 45
<210> 15
<211> 24
<212> PRT
<213> Artificial Sequence
<400> 15
Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu
1 5 10 15
Ser Leu Val Ile Thr Leu Tyr Cys
20
<210> 16
<211> 93
<212> PRT
<213> Artificial Sequence
<400> 16
Met Ile His Leu Gly His Ile Leu Phe Leu Leu Leu Leu Pro Val Ala
1 5 10 15
Ala Ala Gln Thr Thr Pro Gly Glu Arg Ser Ser Leu Pro Ala Phe Tyr
20 25 30
Pro Gly Thr Ser Gly Ser Cys Ser Gly Cys Gly Ser Leu Ser Leu Pro
35 40 45
Leu Leu Ala Gly Leu Val Ala Ala Asp Ala Val Ala Ser Leu Leu Ile
50 55 60
Val Gly Ala Val Phe Leu Cys Ala Arg Pro Arg Arg Ser Pro Ala Gln
65 70 75 80
Glu Asp Gly Lys Val Tyr Ile Asn Met Pro Gly Arg Gly
85 90
<210> 17
<211> 113
<212> PRT
<213> Artificial Sequence
<400> 17
Met Gly Gly Leu Glu Pro Cys Ser Arg Leu Leu Leu Leu Pro Leu Leu
1 5 10 15
Leu Ala Val Ser Gly Leu Arg Pro Val Gln Ala Gln Ala Gln Ser Asp
20 25 30
Cys Ser Cys Ser Thr Val Ser Pro Gly Val Leu Ala Gly Ile Val Met
35 40 45
Gly Asp Leu Val Leu Thr Val Leu Ile Ala Leu Ala Val Tyr Phe Leu
50 55 60
Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg
65 70 75 80
Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly
85 90 95
Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr
100 105 110
Lys
<210> 18
<211> 40
<212> PRT
<213> Artificial Sequence
<400> 18
Leu Arg Pro Val Gln Ala Gln Ala Gln Ser Asp Cys Ser Cys Ser Thr
1 5 10 15
Val Ser Pro Gly Val Leu Ala Gly Ile Val Met Gly Asp Leu Val Leu
20 25 30
Thr Val Leu Ile Ala Leu Ala Val
35 40
<210> 19
<211> 21
<212> PRT
<213> Artificial Sequence
<400> 19
Gly Ser Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu
1 5 10 15
Glu Asn Pro Gly Pro
20
Claims (16)
1.一种新型嵌合受体组合物,其特征在于,包括嵌合抗原受体和包括NKG2D、DAP10和/或DAP12的全长序列或者截短片段的NKG2D嵌合受体。
2.根据权利要求1所述的嵌合受体组合物,其特征在于,包括嵌合抗原受体和NKG2D嵌合受体;所述NKG2D嵌合受体包括NKG2D胞外区和DAP12胞内区序列。
3.根据权利要求2所述的嵌合受体组合物,其特征在于,所述NKG2D嵌合受体还包括一个共刺激分子;所述共刺激分子选自:CD28、4-1BB、DAP10、ICOS、OX40和CD40。
4.根据权利要求1所述的嵌合受体组合物,其特征在于,所述嵌合抗原受体包括:胞外识别区、胞外铰链区、跨膜区和胞内信号区。
5.根据权利要求4所述的嵌合受体组合物,其特征在于,所述嵌合抗原受体的胞外识别区包括识别肿瘤相关抗原或肿瘤特异性抗原的抗体或抗体片段;所述肿瘤相关抗原或肿瘤特异性抗原优选选自:CD19、BCMA、CD22、CD20、CD123、CD30、CD38、CD138、CD56、CD7、CLL-1、CD10、CD34、CS1、CD16、CD4、CD5、IL-1-RAP、ITGB7、k-IgG、TAC1、TRBC1、MUC1、NKG2D、PD-L1、CD133、CD177、LeY、CD70、ROR1、AFP、AXL、CD80、CD86、DLL3、DR5、FAP、LMP1、MAGE-A1、MAGE-A4、MG7、MUC16、PMEL、ROR2、VEGFR2、CD171、Claudin 18.2、Claudin 6、EphA2、ErbB、Fra、PSCA、cMet、IL13Ra2、EPCAM、EGFR、PSMA、EGFRvIII、GPC3、CEA、HER2、GD2和Mesothelin。
6.根据权利要求4所述的嵌合受体组合物,其特征在于,所述铰链区的序列来源于CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80和IgG的至少一种,所述跨膜区的序列来源于CD2、CD27、LFA-1、CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80、CD3ζ和CD3ε的至少一种,所述胞内信号区的序列来源于Toll样受体、CD2、CD27、LFA-1、CD8α、CD28、4-1BB、ICOS、OX40、CD40、CD80、DAP10、DAP12、CD3ζ和CD3ε中的至少一种。
7.根据权利要求1所述的嵌合受体组合物,其特征在于,所述嵌合抗原受体的氨基酸序列为SEQ ID NO.1。
8.根据权利要求1所述的嵌合受体组合物,其特征在于,还包括连接肽,连接所述嵌合抗原受体和嵌合受体;该连接肽为自切割多肽2A肽;该2A肽包括F2A、P2A、T2A和E2A;优选为P2A,其氨基酸序列为SEQ ID NO.10。
9.根据权利要求1所述的嵌合受体组合物,其特征在于,所述嵌合受体的氨基酸序列选自以下序列的一条:SEQ ID NO.2~SEQ ID NO.9;优选为SEQ ID NO.4或SEQ ID NO.7。
10.一种编码如权利要求1-9任一项所述嵌合受体组合物的核酸序列。
11.一种包含如权利要求10所述的核酸序列的载体。
12.一种表达如权利要求1-9任一项所述嵌合受体组合物、含有如权利要求10所述核酸序列或者如权利要求11所述载体的细胞。
13.根据权利要求12所述的细胞,其特征在于,所述细胞选自以下细胞中的一种:T细胞、NK细胞、DC细胞和巨噬细胞;优选为αβT细胞、γδT细胞或NKT细胞。
14.一种治疗肿瘤的生物制剂,其特征在于,包括如权利要求12或13所述的细胞作为主要活性成分。
15.一种如权利要求12或13所述细胞的制备方法,其特征在于,包括将如权利要求11所述载体转染所述细胞的步骤。
16.如权利要求1-9任一项所述的嵌合受体组合物、如权利要求10所述的核酸序列、如权利要求11所述的载体或如权利要求12或13所述的细胞在制备抗肿瘤药物中的应用。
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110793058.6A CN113621073A (zh) | 2021-07-14 | 2021-07-14 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
CN202280008263.XA CN116940670B (zh) | 2021-07-14 | 2022-07-12 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
JP2024502085A JP2024525807A (ja) | 2021-07-14 | 2022-07-12 | 新規キメラ受容体組成物、組換えベクター、細胞およびそれらの応用 |
PCT/CN2022/105029 WO2023284700A1 (zh) | 2021-07-14 | 2022-07-12 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
EP22841336.5A EP4372010A1 (en) | 2021-07-14 | 2022-07-12 | Novel chimeric receptor composition, recombinant vector, cell, and application thereof |
KR1020247001765A KR20240023433A (ko) | 2021-07-14 | 2022-07-12 | 새로운 키메라 수용체 조성물, 재조합 벡터, 세포 및 그 응용 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110793058.6A CN113621073A (zh) | 2021-07-14 | 2021-07-14 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113621073A true CN113621073A (zh) | 2021-11-09 |
Family
ID=78379685
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110793058.6A Withdrawn CN113621073A (zh) | 2021-07-14 | 2021-07-14 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
CN202280008263.XA Active CN116940670B (zh) | 2021-07-14 | 2022-07-12 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202280008263.XA Active CN116940670B (zh) | 2021-07-14 | 2022-07-12 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP4372010A1 (zh) |
JP (1) | JP2024525807A (zh) |
KR (1) | KR20240023433A (zh) |
CN (2) | CN113621073A (zh) |
WO (1) | WO2023284700A1 (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114106199A (zh) * | 2021-11-19 | 2022-03-01 | 广州百暨基因科技有限公司 | 靶向adgre2的嵌合抗原受体及其应用 |
CN114181311A (zh) * | 2021-12-20 | 2022-03-15 | 华东师范大学 | 一种全人源抗DLL3 scFv及其在CART细胞治疗中的应用 |
CN114409782A (zh) * | 2021-12-29 | 2022-04-29 | 华道(上海)生物医药有限公司 | 一种抗IL13Ra2的纳米抗体及其应用 |
WO2023284700A1 (zh) | 2021-07-14 | 2023-01-19 | 苏州易慕峰生物科技有限公司 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
CN117279949A (zh) * | 2022-05-27 | 2023-12-22 | 苏州易慕峰生物科技有限公司 | 包含cldn18.2单域抗体的嵌合抗原受体及其应用 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20240057444A (ko) * | 2017-03-27 | 2024-05-02 | 내셔널 유니버시티 오브 싱가포르 | 절단된 nkg2d 키메라 수용체 및 자연 살해 세포 면역요법에서의 그의 용도 |
CN107759701B (zh) * | 2017-10-27 | 2021-07-02 | 杭州优善生物科技有限公司 | 嵌合抗原受体、其修饰的NK细胞、编码DNA、mRNA、表达载体、制备方法和应用 |
JP2021520780A (ja) * | 2018-04-06 | 2021-08-26 | エイチ リー モフィット キャンサー センター アンド リサーチ インスティテュート インコーポレイテッド | Nkg2dキメラ抗原受容体 |
CN109280087B (zh) * | 2018-10-17 | 2020-05-15 | 新乡医学院 | 一种双靶向转换受体、编码基因、重组表达载体、抗肿瘤nk细胞及其制备方法、应用 |
US20200308248A1 (en) * | 2019-03-26 | 2020-10-01 | ST Phi Therapeutics | Chimeric Natural Killer Cell Receptors and Method of Using Thereof |
CN110698564B (zh) * | 2019-10-12 | 2023-04-07 | 华夏源(上海)细胞基因工程股份有限公司 | 一种双靶点嵌合抗原受体及其表达载体和应用 |
CN110981970B (zh) * | 2019-12-25 | 2023-03-07 | 华夏源(上海)细胞基因工程股份有限公司 | 一种靶向nkg2d配体和cd19的双靶点嵌合抗原受体及其表达载体和应用 |
CN111995688B (zh) * | 2020-08-13 | 2024-01-16 | 金鑫 | 靶向cd123和nkg2d配体的双特异嵌合抗原受体及应用 |
CN113621073A (zh) | 2021-07-14 | 2021-11-09 | 上海易慕峰生物科技有限公司 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
-
2021
- 2021-07-14 CN CN202110793058.6A patent/CN113621073A/zh not_active Withdrawn
-
2022
- 2022-07-12 WO PCT/CN2022/105029 patent/WO2023284700A1/zh active Application Filing
- 2022-07-12 KR KR1020247001765A patent/KR20240023433A/ko unknown
- 2022-07-12 JP JP2024502085A patent/JP2024525807A/ja active Pending
- 2022-07-12 CN CN202280008263.XA patent/CN116940670B/zh active Active
- 2022-07-12 EP EP22841336.5A patent/EP4372010A1/en active Pending
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023284700A1 (zh) | 2021-07-14 | 2023-01-19 | 苏州易慕峰生物科技有限公司 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
CN116940670A (zh) * | 2021-07-14 | 2023-10-24 | 苏州易慕峰生物科技有限公司 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
CN116940670B (zh) * | 2021-07-14 | 2024-07-02 | 苏州易慕峰生物科技有限公司 | 一种新型嵌合受体组合物、重组载体、细胞及其应用 |
CN114106199A (zh) * | 2021-11-19 | 2022-03-01 | 广州百暨基因科技有限公司 | 靶向adgre2的嵌合抗原受体及其应用 |
CN114106199B (zh) * | 2021-11-19 | 2022-07-12 | 广州百暨基因科技有限公司 | 靶向adgre2的嵌合抗原受体及其应用 |
CN114181311A (zh) * | 2021-12-20 | 2022-03-15 | 华东师范大学 | 一种全人源抗DLL3 scFv及其在CART细胞治疗中的应用 |
CN114181311B (zh) * | 2021-12-20 | 2023-06-20 | 华东师范大学 | 一种全人源抗DLL3 scFv及其在CART细胞治疗中的应用 |
CN114409782A (zh) * | 2021-12-29 | 2022-04-29 | 华道(上海)生物医药有限公司 | 一种抗IL13Ra2的纳米抗体及其应用 |
CN114409782B (zh) * | 2021-12-29 | 2023-06-30 | 华道(上海)生物医药有限公司 | 一种抗IL13Ra2的纳米抗体及其应用 |
CN117279949A (zh) * | 2022-05-27 | 2023-12-22 | 苏州易慕峰生物科技有限公司 | 包含cldn18.2单域抗体的嵌合抗原受体及其应用 |
Also Published As
Publication number | Publication date |
---|---|
CN116940670B (zh) | 2024-07-02 |
EP4372010A1 (en) | 2024-05-22 |
JP2024525807A (ja) | 2024-07-12 |
CN116940670A8 (zh) | 2024-01-05 |
CN116940670A (zh) | 2023-10-24 |
WO2023284700A1 (zh) | 2023-01-19 |
KR20240023433A (ko) | 2024-02-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108276493B (zh) | 一种嵌合抗原受体及其应用 | |
CN103483452B (zh) | 双信号独立的嵌合抗原受体及其用途 | |
CN110372796B (zh) | 靶向bcma的嵌合抗原受体及其制法和应用 | |
CN112673025B (zh) | 一种包含第三信号受体的嵌合抗原受体及其应用 | |
CN113621073A (zh) | 一种新型嵌合受体组合物、重组载体、细胞及其应用 | |
CN113784732B (zh) | 靶向bcma的工程化免疫细胞及其用途 | |
EP3964238A1 (en) | Bcma-targeting engineered immune cell and use thereof | |
CN108064252A (zh) | 嵌合抗原受体及其使用方法 | |
WO2017176525A1 (en) | Car having replicated binding motifs in a co-stimulatory domain | |
WO2022032864A1 (zh) | 一种识别Fc片段的嵌合抗原受体及其应用 | |
CN112480258B (zh) | 抗cd123纳米抗体及其应用 | |
CN111411085A (zh) | 一种嵌合抗原受体t细胞及其应用 | |
WO2023109257A1 (zh) | 人源化的bcma抗体和bcma-car-t/bcma-car-dnt细胞 | |
CN117024598A (zh) | 长效的Meso-B7H3双靶点嵌合抗原受体及其应用 | |
CN116814664B (zh) | 一种扩展肿瘤识别表位的cea嵌合抗原受体t细胞的制备与应用 | |
CN113637087A (zh) | 一种提高细胞免疫疗法安全性的嵌合受体和细胞 | |
WO2020259541A1 (zh) | 一种用于肿瘤治疗的嵌合抗原受体t淋巴细胞及其制备方法与应用 | |
CN112442508B (zh) | 靶向cd22和cd19的嵌合抗原受体及其应用 | |
EP4141118A1 (en) | Technique for preparing universal humanised car19-dnt cells and application therefor | |
CN118055944A (zh) | 调节Bcl-2增强嵌合抗原受体癌症免疫疗法功效 | |
CN112673024B (zh) | 一种包含共刺激受体的嵌合抗原受体及应用 | |
CN113528452A (zh) | 共表达IL-21和hrCD16嵌合受体的免疫细胞及其应用 | |
WO2020154627A1 (en) | Epcam antibody and epcam-car-t cells | |
WO2024011335A1 (zh) | 经修饰的免疫细胞 | |
CN117305248A (zh) | 抗EGFR和cMet双特异性嵌合抗原受体及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WW01 | Invention patent application withdrawn after publication |
Application publication date: 20211109 |
|
WW01 | Invention patent application withdrawn after publication |