CN107056952A - Cea.car‑t及其制备与应用 - Google Patents
Cea.car‑t及其制备与应用 Download PDFInfo
- Publication number
- CN107056952A CN107056952A CN201710326932.9A CN201710326932A CN107056952A CN 107056952 A CN107056952 A CN 107056952A CN 201710326932 A CN201710326932 A CN 201710326932A CN 107056952 A CN107056952 A CN 107056952A
- Authority
- CN
- China
- Prior art keywords
- chimeric antigen
- gly
- antigen
- ser
- leu
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 239000000427 antigen Substances 0.000 claims abstract description 73
- 108091007433 antigens Proteins 0.000 claims abstract description 73
- 102000036639 antigens Human genes 0.000 claims abstract description 73
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 61
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 26
- 230000008685 targeting Effects 0.000 claims abstract description 26
- 230000003834 intracellular effect Effects 0.000 claims abstract description 22
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims abstract description 18
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims abstract description 18
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 16
- 229920001184 polypeptide Polymers 0.000 claims abstract description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 13
- 210000004027 cell Anatomy 0.000 claims description 60
- 239000012634 fragment Substances 0.000 claims description 19
- 230000014509 gene expression Effects 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 15
- 108060003951 Immunoglobulin Proteins 0.000 claims description 12
- 102000018358 immunoglobulin Human genes 0.000 claims description 12
- 239000013604 expression vector Substances 0.000 claims description 9
- 230000000259 anti-tumor effect Effects 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 108091033319 polynucleotide Proteins 0.000 claims description 6
- 239000002157 polynucleotide Substances 0.000 claims description 6
- 102000040430 polynucleotide Human genes 0.000 claims description 6
- 210000004899 c-terminal region Anatomy 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 210000001161 mammalian embryo Anatomy 0.000 claims 5
- 230000001093 anti-cancer Effects 0.000 claims 2
- 102000010910 CD28 Antigens Human genes 0.000 claims 1
- 108010062433 CD28 Antigens Proteins 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 abstract description 5
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 abstract 1
- 241000700605 Viruses Species 0.000 description 35
- 150000001413 amino acids Chemical group 0.000 description 25
- 239000002773 nucleotide Substances 0.000 description 16
- 125000003729 nucleotide group Chemical group 0.000 description 16
- 108020004414 DNA Proteins 0.000 description 12
- 239000001963 growth medium Substances 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 11
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 230000003612 virological effect Effects 0.000 description 9
- 241000880493 Leptailurus serval Species 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 6
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 102100037850 Interferon gamma Human genes 0.000 description 5
- 108010074328 Interferon-gamma Proteins 0.000 description 5
- 108010078144 glutaminyl-glycine Proteins 0.000 description 5
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- AOHKLEBWKMKITA-IHRRRGAJSA-N Arg-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](CCCN=C(N)N)N AOHKLEBWKMKITA-IHRRRGAJSA-N 0.000 description 4
- 238000011357 CAR T-cell therapy Methods 0.000 description 4
- 108010077544 Chromatin Proteins 0.000 description 4
- 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 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 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 4
- 108010087924 alanylproline Proteins 0.000 description 4
- 108010047857 aspartylglycine Proteins 0.000 description 4
- 210000003483 chromatin Anatomy 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 4
- 230000002147 killing effect Effects 0.000 description 4
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 108010070643 prolylglutamic acid Proteins 0.000 description 4
- XUCHENWTTBFODJ-FXQIFTODSA-N Ala-Met-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O XUCHENWTTBFODJ-FXQIFTODSA-N 0.000 description 3
- 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 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
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- BPHKULHWEIUDOB-FXQIFTODSA-N Cys-Gln-Gln Chemical compound SC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BPHKULHWEIUDOB-FXQIFTODSA-N 0.000 description 3
- 108010065920 Insulin Lispro Proteins 0.000 description 3
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 3
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 3
- HPBCTWSUJOGJSH-MNXVOIDGSA-N Leu-Glu-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O HPBCTWSUJOGJSH-MNXVOIDGSA-N 0.000 description 3
- 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 3
- KWUKZRFFKPLUPE-HJGDQZAQSA-N Lys-Asp-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KWUKZRFFKPLUPE-HJGDQZAQSA-N 0.000 description 3
- VVURYEVJJTXWNE-ULQDDVLXSA-N Lys-Tyr-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O VVURYEVJJTXWNE-ULQDDVLXSA-N 0.000 description 3
- 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 3
- KIEPQOIQHFKQLK-PCBIJLKTSA-N Phe-Asn-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KIEPQOIQHFKQLK-PCBIJLKTSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- JMVQDLDPDBXAAX-YUMQZZPRSA-N Pro-Gly-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 JMVQDLDPDBXAAX-YUMQZZPRSA-N 0.000 description 3
- OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 3
- IOVHBRCQOGWAQH-ZKWXMUAHSA-N Ser-Gly-Ile Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(O)=O IOVHBRCQOGWAQH-ZKWXMUAHSA-N 0.000 description 3
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 3
- WLJPJRGQRNCIQS-ZLUOBGJFSA-N Ser-Ser-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O WLJPJRGQRNCIQS-ZLUOBGJFSA-N 0.000 description 3
- UKKROEYWYIHWBD-ZKWXMUAHSA-N Ser-Val-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O UKKROEYWYIHWBD-ZKWXMUAHSA-N 0.000 description 3
- XSLXHSYIVPGEER-KZVJFYERSA-N Thr-Ala-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O XSLXHSYIVPGEER-KZVJFYERSA-N 0.000 description 3
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-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
- 108010081404 acein-2 Proteins 0.000 description 3
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 3
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 3
- 108010068380 arginylarginine Proteins 0.000 description 3
- 108010062796 arginyllysine Proteins 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000005017 genetic modification Effects 0.000 description 3
- 235000013617 genetically modified food Nutrition 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 201000002313 intestinal cancer Diseases 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 108010070409 phenylalanyl-glycyl-glycine Proteins 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- BTYTYHBSJKQBQA-GCJQMDKQSA-N Ala-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)O BTYTYHBSJKQBQA-GCJQMDKQSA-N 0.000 description 2
- BEMGNWZECGIJOI-WDSKDSINSA-N Ala-Gly-Glu Chemical compound [H]N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O BEMGNWZECGIJOI-WDSKDSINSA-N 0.000 description 2
- DPNZTBKGAUAZQU-DLOVCJGASA-N Ala-Leu-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N DPNZTBKGAUAZQU-DLOVCJGASA-N 0.000 description 2
- RTZCUEHYUQZIDE-WHFBIAKZSA-N Ala-Ser-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RTZCUEHYUQZIDE-WHFBIAKZSA-N 0.000 description 2
- 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 2
- ISCYZXFOCXWUJU-KZVJFYERSA-N Ala-Thr-Met Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCSC)C(O)=O ISCYZXFOCXWUJU-KZVJFYERSA-N 0.000 description 2
- ZJLORAAXDAJLDC-CQDKDKBSSA-N Ala-Tyr-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O ZJLORAAXDAJLDC-CQDKDKBSSA-N 0.000 description 2
- GIVATXIGCXFQQA-FXQIFTODSA-N Arg-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N GIVATXIGCXFQQA-FXQIFTODSA-N 0.000 description 2
- 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 2
- YKBHOXLMMPZPHQ-GMOBBJLQSA-N Arg-Ile-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O YKBHOXLMMPZPHQ-GMOBBJLQSA-N 0.000 description 2
- LXMKTIZAGIBQRX-HRCADAONSA-N Arg-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O LXMKTIZAGIBQRX-HRCADAONSA-N 0.000 description 2
- 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 2
- HCAUEJAQCXVQQM-ACZMJKKPSA-N Asn-Glu-Asp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HCAUEJAQCXVQQM-ACZMJKKPSA-N 0.000 description 2
- HDHZCEDPLTVHFZ-GUBZILKMSA-N Asn-Leu-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O HDHZCEDPLTVHFZ-GUBZILKMSA-N 0.000 description 2
- USNJAPJZSGTTPX-XVSYOHENSA-N Asp-Phe-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O USNJAPJZSGTTPX-XVSYOHENSA-N 0.000 description 2
- AHWRSSLYSGLBGD-CIUDSAMLSA-N Asp-Pro-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AHWRSSLYSGLBGD-CIUDSAMLSA-N 0.000 description 2
- DINOVZWPTMGSRF-QXEWZRGKSA-N Asp-Pro-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O DINOVZWPTMGSRF-QXEWZRGKSA-N 0.000 description 2
- JDDYEZGPYBBPBN-JRQIVUDYSA-N Asp-Thr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JDDYEZGPYBBPBN-JRQIVUDYSA-N 0.000 description 2
- XWKBWZXGNXTDKY-ZKWXMUAHSA-N Asp-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O XWKBWZXGNXTDKY-ZKWXMUAHSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- KABHAOSDMIYXTR-GUBZILKMSA-N Cys-Glu-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)N KABHAOSDMIYXTR-GUBZILKMSA-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
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 2
- MADFVRSKEIEZHZ-DCAQKATOSA-N Gln-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N MADFVRSKEIEZHZ-DCAQKATOSA-N 0.000 description 2
- RBWKVOSARCFSQQ-FXQIFTODSA-N Gln-Gln-Ser Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O RBWKVOSARCFSQQ-FXQIFTODSA-N 0.000 description 2
- KCJJFESQRXGTGC-BQBZGAKWSA-N Gln-Glu-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O KCJJFESQRXGTGC-BQBZGAKWSA-N 0.000 description 2
- MLSKFHLRFVGNLL-WDCWCFNPSA-N Gln-Leu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MLSKFHLRFVGNLL-WDCWCFNPSA-N 0.000 description 2
- SYZZMPFLOLSMHL-XHNCKOQMSA-N Gln-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N)C(=O)O SYZZMPFLOLSMHL-XHNCKOQMSA-N 0.000 description 2
- WZZSKAJIHTUUSG-ACZMJKKPSA-N Glu-Ala-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O WZZSKAJIHTUUSG-ACZMJKKPSA-N 0.000 description 2
- NKLRYVLERDYDBI-FXQIFTODSA-N Glu-Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NKLRYVLERDYDBI-FXQIFTODSA-N 0.000 description 2
- BUZMZDDKFCSKOT-CIUDSAMLSA-N Glu-Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O BUZMZDDKFCSKOT-CIUDSAMLSA-N 0.000 description 2
- OAGVHWYIBZMWLA-YFKPBYRVSA-N Glu-Gly-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)NCC(O)=O OAGVHWYIBZMWLA-YFKPBYRVSA-N 0.000 description 2
- MFVQGXGQRIXBPK-WDSKDSINSA-N Gly-Ala-Glu Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFVQGXGQRIXBPK-WDSKDSINSA-N 0.000 description 2
- LJPIRKICOISLKN-WHFBIAKZSA-N Gly-Ala-Ser Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O LJPIRKICOISLKN-WHFBIAKZSA-N 0.000 description 2
- XCLCVBYNGXEVDU-WHFBIAKZSA-N Gly-Asn-Ser Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O XCLCVBYNGXEVDU-WHFBIAKZSA-N 0.000 description 2
- XBWMTPAIUQIWKA-BYULHYEWSA-N Gly-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CN XBWMTPAIUQIWKA-BYULHYEWSA-N 0.000 description 2
- 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 2
- VBOBNHSVQKKTOT-YUMQZZPRSA-N Gly-Lys-Ala Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O VBOBNHSVQKKTOT-YUMQZZPRSA-N 0.000 description 2
- JPVGHHQGKPQYIL-KBPBESRZSA-N Gly-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 JPVGHHQGKPQYIL-KBPBESRZSA-N 0.000 description 2
- JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 2
- XHVONGZZVUUORG-WEDXCCLWSA-N Gly-Thr-Lys Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN XHVONGZZVUUORG-WEDXCCLWSA-N 0.000 description 2
- FFALDIDGPLUDKV-ZDLURKLDSA-N Gly-Thr-Ser Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O FFALDIDGPLUDKV-ZDLURKLDSA-N 0.000 description 2
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 2
- FOCSWPCHUDVNLP-PMVMPFDFSA-N His-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](CC4=CN=CN4)N FOCSWPCHUDVNLP-PMVMPFDFSA-N 0.000 description 2
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- SEMUSFOBZGKBGW-YTFOTSKYSA-N Leu-Ile-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O SEMUSFOBZGKBGW-YTFOTSKYSA-N 0.000 description 2
- NRFGTHFONZYFNY-MGHWNKPDSA-N Leu-Ile-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NRFGTHFONZYFNY-MGHWNKPDSA-N 0.000 description 2
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 2
- 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 2
- ARNIBBOXIAWUOP-MGHWNKPDSA-N Leu-Tyr-Ile 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@@H](C)CC)C(O)=O ARNIBBOXIAWUOP-MGHWNKPDSA-N 0.000 description 2
- MQMIRLVJXQNTRJ-SDDRHHMPSA-N Lys-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N)C(=O)O MQMIRLVJXQNTRJ-SDDRHHMPSA-N 0.000 description 2
- HVAUKHLDSDDROB-KKUMJFAQSA-N Lys-Lys-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O HVAUKHLDSDDROB-KKUMJFAQSA-N 0.000 description 2
- PIXVFCBYEGPZPA-JYJNAYRXSA-N Lys-Phe-Gln Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)N PIXVFCBYEGPZPA-JYJNAYRXSA-N 0.000 description 2
- ABHVWYPPHDYFNY-WDSOQIARSA-N Met-His-Trp Chemical compound C([C@H](NC(=O)[C@@H](N)CCSC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CN=CN1 ABHVWYPPHDYFNY-WDSOQIARSA-N 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- NAXPHWZXEXNDIW-JTQLQIEISA-N Phe-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 NAXPHWZXEXNDIW-JTQLQIEISA-N 0.000 description 2
- HNFUGJUZJRYUHN-JSGCOSHPSA-N Phe-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=CC=C1 HNFUGJUZJRYUHN-JSGCOSHPSA-N 0.000 description 2
- IEOHQGFKHXUALJ-JYJNAYRXSA-N Phe-Met-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IEOHQGFKHXUALJ-JYJNAYRXSA-N 0.000 description 2
- JDMKQHSHKJHAHR-UHFFFAOYSA-N Phe-Phe-Leu-Tyr Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)CC1=CC=CC=C1 JDMKQHSHKJHAHR-UHFFFAOYSA-N 0.000 description 2
- DBALDZKOTNSBFM-FXQIFTODSA-N Pro-Ala-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O DBALDZKOTNSBFM-FXQIFTODSA-N 0.000 description 2
- IHCXPSYCHXFXKT-DCAQKATOSA-N Pro-Arg-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O IHCXPSYCHXFXKT-DCAQKATOSA-N 0.000 description 2
- 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 2
- VPEVBAUSTBWQHN-NHCYSSNCSA-N Pro-Glu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O VPEVBAUSTBWQHN-NHCYSSNCSA-N 0.000 description 2
- RMODQFBNDDENCP-IHRRRGAJSA-N Pro-Lys-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O RMODQFBNDDENCP-IHRRRGAJSA-N 0.000 description 2
- AJBQTGZIZQXBLT-STQMWFEESA-N Pro-Phe-Gly Chemical compound C([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 AJBQTGZIZQXBLT-STQMWFEESA-N 0.000 description 2
- PCWLNNZTBJTZRN-AVGNSLFASA-N Pro-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 PCWLNNZTBJTZRN-AVGNSLFASA-N 0.000 description 2
- QKWYXRPICJEQAJ-KJEVXHAQSA-N Pro-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@@H]2CCCN2)O QKWYXRPICJEQAJ-KJEVXHAQSA-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
- 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
- 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 2
- MPPHJZYXDVDGOF-BWBBJGPYSA-N Ser-Cys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CO MPPHJZYXDVDGOF-BWBBJGPYSA-N 0.000 description 2
- ZOHGLPQGEHSLPD-FXQIFTODSA-N Ser-Gln-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ZOHGLPQGEHSLPD-FXQIFTODSA-N 0.000 description 2
- HJEBZBMOTCQYDN-ACZMJKKPSA-N Ser-Glu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HJEBZBMOTCQYDN-ACZMJKKPSA-N 0.000 description 2
- GYDFRTRSSXOZCR-ACZMJKKPSA-N Ser-Ser-Glu Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O GYDFRTRSSXOZCR-ACZMJKKPSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- GXUWHVZYDAHFSV-FLBSBUHZSA-N Thr-Ile-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GXUWHVZYDAHFSV-FLBSBUHZSA-N 0.000 description 2
- MFMGPEKYBXFIRF-SUSMZKCASA-N Thr-Thr-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MFMGPEKYBXFIRF-SUSMZKCASA-N 0.000 description 2
- YOPQYBJJNSIQGZ-JNPHEJMOSA-N Thr-Tyr-Tyr Chemical compound C([C@H](NC(=O)[C@@H](N)[C@H](O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 YOPQYBJJNSIQGZ-JNPHEJMOSA-N 0.000 description 2
- 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 2
- KIMOCKLJBXHFIN-YLVFBTJISA-N Trp-Ile-Gly Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O)=CNC2=C1 KIMOCKLJBXHFIN-YLVFBTJISA-N 0.000 description 2
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 2
- 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 2
- SMLCYZYQFRTLCO-UWJYBYFXSA-N Tyr-Cys-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O SMLCYZYQFRTLCO-UWJYBYFXSA-N 0.000 description 2
- QUILOGWWLXMSAT-IHRRRGAJSA-N Tyr-Gln-Gln Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O QUILOGWWLXMSAT-IHRRRGAJSA-N 0.000 description 2
- UUJHRSTVQCFDPA-UFYCRDLUSA-N Tyr-Tyr-Val Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 UUJHRSTVQCFDPA-UFYCRDLUSA-N 0.000 description 2
- VFOHXOLPLACADK-GVXVVHGQSA-N Val-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N VFOHXOLPLACADK-GVXVVHGQSA-N 0.000 description 2
- WBAJDGWKRIHOAC-GVXVVHGQSA-N Val-Lys-Gln Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O WBAJDGWKRIHOAC-GVXVVHGQSA-N 0.000 description 2
- ZRSZTKTVPNSUNA-IHRRRGAJSA-N Val-Lys-Leu Chemical compound CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)C(C)C)C(O)=O ZRSZTKTVPNSUNA-IHRRRGAJSA-N 0.000 description 2
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 108010052670 arginyl-glutamyl-glutamic acid Proteins 0.000 description 2
- 108010060035 arginylproline Proteins 0.000 description 2
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 2
- 108010093581 aspartyl-proline Proteins 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 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 2
- 108010050475 glycyl-leucyl-tyrosine Proteins 0.000 description 2
- 108010050848 glycylleucine Proteins 0.000 description 2
- 108010015792 glycyllysine Proteins 0.000 description 2
- 108010087823 glycyltyrosine Proteins 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 108010078274 isoleucylvaline Proteins 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 108010064235 lysylglycine Proteins 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 108010051242 phenylalanylserine Proteins 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000012096 transfection reagent Substances 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 108010052774 valyl-lysyl-glycyl-phenylalanyl-tyrosine Proteins 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108010000998 wheylin-2 peptide Proteins 0.000 description 2
- COEXAQSTZUWMRI-STQMWFEESA-N (2s)-1-[2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([C@H](N)C(=O)NCC(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=C(O)C=C1 COEXAQSTZUWMRI-STQMWFEESA-N 0.000 description 1
- IESDGNYHXIOKRW-YXMSTPNBSA-N (2s)-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s,3r)-2-amino-3-hydroxybutanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IESDGNYHXIOKRW-YXMSTPNBSA-N 0.000 description 1
- DIBLBAURNYJYBF-XLXZRNDBSA-N (2s)-2-[[(2s)-2-[[2-[[(2s)-6-amino-2-[[(2s)-2-amino-3-methylbutanoyl]amino]hexanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 DIBLBAURNYJYBF-XLXZRNDBSA-N 0.000 description 1
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 1
- 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
- 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
- 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 1
- OINVDEKBKBCPLX-JXUBOQSCSA-N Ala-Lys-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OINVDEKBKBCPLX-JXUBOQSCSA-N 0.000 description 1
- 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 1
- IPZQNYYAYVRKKK-FXQIFTODSA-N Ala-Pro-Ala Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O IPZQNYYAYVRKKK-FXQIFTODSA-N 0.000 description 1
- IORKCNUBHNIMKY-CIUDSAMLSA-N Ala-Pro-Glu Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O IORKCNUBHNIMKY-CIUDSAMLSA-N 0.000 description 1
- GMGWOTQMUKYZIE-UBHSHLNASA-N Ala-Pro-Phe Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 GMGWOTQMUKYZIE-UBHSHLNASA-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
- CREYEAPXISDKSB-FQPOAREZSA-N Ala-Thr-Tyr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CREYEAPXISDKSB-FQPOAREZSA-N 0.000 description 1
- KWKQGHSSNHPGOW-BQBZGAKWSA-N Arg-Ala-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(O)=O KWKQGHSSNHPGOW-BQBZGAKWSA-N 0.000 description 1
- OTOXOKCIIQLMFH-KZVJFYERSA-N Arg-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N OTOXOKCIIQLMFH-KZVJFYERSA-N 0.000 description 1
- HJVGMOYJDDXLMI-AVGNSLFASA-N Arg-Arg-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CCCNC(N)=N HJVGMOYJDDXLMI-AVGNSLFASA-N 0.000 description 1
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 1
- PNQWAUXQDBIJDY-GUBZILKMSA-N Arg-Glu-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PNQWAUXQDBIJDY-GUBZILKMSA-N 0.000 description 1
- PHHRSPBBQUFULD-UWVGGRQHSA-N Arg-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N PHHRSPBBQUFULD-UWVGGRQHSA-N 0.000 description 1
- WCZXPVPHUMYLMS-VEVYYDQMSA-N Arg-Thr-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O WCZXPVPHUMYLMS-VEVYYDQMSA-N 0.000 description 1
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-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
- SLKLLQWZQHXYSV-CIUDSAMLSA-N Asn-Ala-Lys Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O SLKLLQWZQHXYSV-CIUDSAMLSA-N 0.000 description 1
- BVLIJXXSXBUGEC-SRVKXCTJSA-N Asn-Asn-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BVLIJXXSXBUGEC-SRVKXCTJSA-N 0.000 description 1
- WPOLSNAQGVHROR-GUBZILKMSA-N Asn-Gln-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)N WPOLSNAQGVHROR-GUBZILKMSA-N 0.000 description 1
- DXVMJJNAOVECBA-WHFBIAKZSA-N Asn-Gly-Asn Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O DXVMJJNAOVECBA-WHFBIAKZSA-N 0.000 description 1
- OLVIPTLKNSAYRJ-YUMQZZPRSA-N Asn-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N OLVIPTLKNSAYRJ-YUMQZZPRSA-N 0.000 description 1
- WQLJRNRLHWJIRW-KKUMJFAQSA-N Asn-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)N)N)O WQLJRNRLHWJIRW-KKUMJFAQSA-N 0.000 description 1
- NYGILGUOUOXGMJ-YUMQZZPRSA-N Asn-Lys-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O NYGILGUOUOXGMJ-YUMQZZPRSA-N 0.000 description 1
- XMHFCUKJRCQXGI-CIUDSAMLSA-N Asn-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)N)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O XMHFCUKJRCQXGI-CIUDSAMLSA-N 0.000 description 1
- HNXWVVHIGTZTBO-LKXGYXEUSA-N Asn-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O HNXWVVHIGTZTBO-LKXGYXEUSA-N 0.000 description 1
- 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 1
- KBQOUDLMWYWXNP-YDHLFZDLSA-N Asn-Val-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KBQOUDLMWYWXNP-YDHLFZDLSA-N 0.000 description 1
- PXLNPFOJZQMXAT-BYULHYEWSA-N Asp-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC(O)=O PXLNPFOJZQMXAT-BYULHYEWSA-N 0.000 description 1
- QCVXMEHGFUMKCO-YUMQZZPRSA-N Asp-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(O)=O QCVXMEHGFUMKCO-YUMQZZPRSA-N 0.000 description 1
- 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 1
- WSGVTKZFVJSJOG-RCOVLWMOSA-N Asp-Gly-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O WSGVTKZFVJSJOG-RCOVLWMOSA-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
- KPSHWSWFPUDEGF-FXQIFTODSA-N Asp-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(O)=O KPSHWSWFPUDEGF-FXQIFTODSA-N 0.000 description 1
- GGRSYTUJHAZTFN-IHRRRGAJSA-N Asp-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O GGRSYTUJHAZTFN-IHRRRGAJSA-N 0.000 description 1
- CUQDCPXNZPDYFQ-ZLUOBGJFSA-N Asp-Ser-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O CUQDCPXNZPDYFQ-ZLUOBGJFSA-N 0.000 description 1
- YUELDQUPTAYEGM-XIRDDKMYSA-N Asp-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CC(=O)O)N YUELDQUPTAYEGM-XIRDDKMYSA-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
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 102100027207 CD27 antigen Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OHLLDUNVMPPUMD-DCAQKATOSA-N Cys-Leu-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N OHLLDUNVMPPUMD-DCAQKATOSA-N 0.000 description 1
- ZXCAQANTQWBICD-DCAQKATOSA-N Cys-Lys-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)N ZXCAQANTQWBICD-DCAQKATOSA-N 0.000 description 1
- SMEYEQDCCBHTEF-FXQIFTODSA-N Cys-Pro-Ala Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O SMEYEQDCCBHTEF-FXQIFTODSA-N 0.000 description 1
- KSMSFCBQBQPFAD-GUBZILKMSA-N Cys-Pro-Pro Chemical compound SC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 KSMSFCBQBQPFAD-GUBZILKMSA-N 0.000 description 1
- ALTQTAKGRFLRLR-GUBZILKMSA-N Cys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N ALTQTAKGRFLRLR-GUBZILKMSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 238000002965 ELISA Methods 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
- 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
- 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
- DHNWZLGBTPUTQQ-QEJZJMRPSA-N Gln-Asp-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N DHNWZLGBTPUTQQ-QEJZJMRPSA-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
- CGVWDTRDPLOMHZ-FXQIFTODSA-N Gln-Glu-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O CGVWDTRDPLOMHZ-FXQIFTODSA-N 0.000 description 1
- XSBGUANSZDGULP-IUCAKERBSA-N Gln-Gly-Lys Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(O)=O XSBGUANSZDGULP-IUCAKERBSA-N 0.000 description 1
- JXFLPKSDLDEOQK-JHEQGTHGSA-N Gln-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O JXFLPKSDLDEOQK-JHEQGTHGSA-N 0.000 description 1
- LGIKBBLQVSWUGK-DCAQKATOSA-N Gln-Leu-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGIKBBLQVSWUGK-DCAQKATOSA-N 0.000 description 1
- AQPZYBSRDRZBAG-AVGNSLFASA-N Gln-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)N)N AQPZYBSRDRZBAG-AVGNSLFASA-N 0.000 description 1
- HMIXCETWRYDVMO-GUBZILKMSA-N Gln-Pro-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O HMIXCETWRYDVMO-GUBZILKMSA-N 0.000 description 1
- OSCLNNWLKKIQJM-WDSKDSINSA-N Gln-Ser-Gly Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O OSCLNNWLKKIQJM-WDSKDSINSA-N 0.000 description 1
- CSMHMEATMDCQNY-DZKIICNBSA-N Gln-Val-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CSMHMEATMDCQNY-DZKIICNBSA-N 0.000 description 1
- ITYRYNUZHPNCIK-GUBZILKMSA-N Glu-Ala-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O ITYRYNUZHPNCIK-GUBZILKMSA-N 0.000 description 1
- KBKGRMNVKPSQIF-XDTLVQLUSA-N Glu-Ala-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O KBKGRMNVKPSQIF-XDTLVQLUSA-N 0.000 description 1
- GLWXKFRTOHKGIT-ACZMJKKPSA-N Glu-Asn-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O GLWXKFRTOHKGIT-ACZMJKKPSA-N 0.000 description 1
- RFDHKPSHTXZKLL-IHRRRGAJSA-N Glu-Gln-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)O)N RFDHKPSHTXZKLL-IHRRRGAJSA-N 0.000 description 1
- HNVFSTLPVJWIDV-CIUDSAMLSA-N Glu-Glu-Gln Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O HNVFSTLPVJWIDV-CIUDSAMLSA-N 0.000 description 1
- KASDBWKLWJKTLJ-GUBZILKMSA-N Glu-Glu-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O KASDBWKLWJKTLJ-GUBZILKMSA-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
- VMKCPNBBPGGQBJ-GUBZILKMSA-N Glu-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N VMKCPNBBPGGQBJ-GUBZILKMSA-N 0.000 description 1
- 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 1
- QMOSCLNJVKSHHU-YUMQZZPRSA-N Glu-Met-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)NCC(O)=O QMOSCLNJVKSHHU-YUMQZZPRSA-N 0.000 description 1
- YHOJJFFTSMWVGR-HJGDQZAQSA-N Glu-Met-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O YHOJJFFTSMWVGR-HJGDQZAQSA-N 0.000 description 1
- AAJHGGDRKHYSDH-GUBZILKMSA-N Glu-Pro-Gln Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O AAJHGGDRKHYSDH-GUBZILKMSA-N 0.000 description 1
- ALMBZBOCGSVSAI-ACZMJKKPSA-N Glu-Ser-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ALMBZBOCGSVSAI-ACZMJKKPSA-N 0.000 description 1
- 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 1
- BPCLDCNZBUYGOD-BPUTZDHNSA-N Glu-Trp-Glu Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 BPCLDCNZBUYGOD-BPUTZDHNSA-N 0.000 description 1
- JVZLZVJTIXVIHK-SXNHZJKMSA-N Glu-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCC(=O)O)N JVZLZVJTIXVIHK-SXNHZJKMSA-N 0.000 description 1
- MFYLRRCYBBJYPI-JYJNAYRXSA-N Glu-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O MFYLRRCYBBJYPI-JYJNAYRXSA-N 0.000 description 1
- ZALGPUWUVHOGAE-GVXVVHGQSA-N Glu-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZALGPUWUVHOGAE-GVXVVHGQSA-N 0.000 description 1
- WGYHAAXZWPEBDQ-IFFSRLJSSA-N Glu-Val-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WGYHAAXZWPEBDQ-IFFSRLJSSA-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
- OCQUNKSFDYDXBG-QXEWZRGKSA-N Gly-Arg-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OCQUNKSFDYDXBG-QXEWZRGKSA-N 0.000 description 1
- GRIRDMVMJJDZKV-RCOVLWMOSA-N Gly-Asn-Val Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O GRIRDMVMJJDZKV-RCOVLWMOSA-N 0.000 description 1
- PABFFPWEJMEVEC-JGVFFNPUSA-N Gly-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)CN)C(=O)O PABFFPWEJMEVEC-JGVFFNPUSA-N 0.000 description 1
- 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 1
- BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 1
- UQJNXZSSGQIPIQ-FBCQKBJTSA-N Gly-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)CN UQJNXZSSGQIPIQ-FBCQKBJTSA-N 0.000 description 1
- VAXIVIPMCTYSHI-YUMQZZPRSA-N Gly-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)CN VAXIVIPMCTYSHI-YUMQZZPRSA-N 0.000 description 1
- UUYBFNKHOCJCHT-VHSXEESVSA-N Gly-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN UUYBFNKHOCJCHT-VHSXEESVSA-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
- GMTXWRIDLGTVFC-IUCAKERBSA-N Gly-Lys-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GMTXWRIDLGTVFC-IUCAKERBSA-N 0.000 description 1
- WDEHMRNSGHVNOH-VHSXEESVSA-N Gly-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)CN)C(=O)O WDEHMRNSGHVNOH-VHSXEESVSA-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
- OOCFXNOVSLSHAB-IUCAKERBSA-N Gly-Pro-Pro Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OOCFXNOVSLSHAB-IUCAKERBSA-N 0.000 description 1
- 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 1
- JSLVAHYTAJJEQH-QWRGUYRKSA-N Gly-Ser-Phe Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JSLVAHYTAJJEQH-QWRGUYRKSA-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
- NGBGZCUWFVVJKC-IRXDYDNUSA-N Gly-Tyr-Tyr Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 NGBGZCUWFVVJKC-IRXDYDNUSA-N 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 102100022132 High affinity immunoglobulin epsilon receptor subunit gamma Human genes 0.000 description 1
- 108091010847 High affinity immunoglobulin epsilon receptor subunit gamma Proteins 0.000 description 1
- WMKXFMUJRCEGRP-SRVKXCTJSA-N His-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N WMKXFMUJRCEGRP-SRVKXCTJSA-N 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- NPROWIBAWYMPAZ-GUDRVLHUSA-N Ile-Asp-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N NPROWIBAWYMPAZ-GUDRVLHUSA-N 0.000 description 1
- DFJJAVZIHDFOGQ-MNXVOIDGSA-N Ile-Glu-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N DFJJAVZIHDFOGQ-MNXVOIDGSA-N 0.000 description 1
- LWWILHPVAKKLQS-QXEWZRGKSA-N Ile-Gly-Met Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCSC)C(=O)O)N LWWILHPVAKKLQS-QXEWZRGKSA-N 0.000 description 1
- DMSVBUWGDLYNLC-IAVJCBSLSA-N Ile-Ile-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 DMSVBUWGDLYNLC-IAVJCBSLSA-N 0.000 description 1
- UAELWXJFLZBKQS-WHOFXGATSA-N Ile-Phe-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(O)=O UAELWXJFLZBKQS-WHOFXGATSA-N 0.000 description 1
- 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 1
- UYODHPPSCXBNCS-XUXIUFHCSA-N Ile-Val-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(C)C UYODHPPSCXBNCS-XUXIUFHCSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- RCFDOSNHHZGBOY-UHFFFAOYSA-N L-isoleucyl-L-alanine Natural products CCC(C)C(N)C(=O)NC(C)C(O)=O RCFDOSNHHZGBOY-UHFFFAOYSA-N 0.000 description 1
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-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
- MYGQXVYRZMKRDB-SRVKXCTJSA-N Leu-Asp-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN MYGQXVYRZMKRDB-SRVKXCTJSA-N 0.000 description 1
- PVMPDMIKUVNOBD-CIUDSAMLSA-N Leu-Asp-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O PVMPDMIKUVNOBD-CIUDSAMLSA-N 0.000 description 1
- LOLUPZNNADDTAA-AVGNSLFASA-N Leu-Gln-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LOLUPZNNADDTAA-AVGNSLFASA-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
- FIYMBBHGYNQFOP-IUCAKERBSA-N Leu-Gly-Gln Chemical compound CC(C)C[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)N)C(=O)O)N FIYMBBHGYNQFOP-IUCAKERBSA-N 0.000 description 1
- VWHGTYCRDRBSFI-ZETCQYMHSA-N Leu-Gly-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)NCC(O)=O VWHGTYCRDRBSFI-ZETCQYMHSA-N 0.000 description 1
- BKTXKJMNTSMJDQ-AVGNSLFASA-N Leu-His-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N BKTXKJMNTSMJDQ-AVGNSLFASA-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
- LKXANTUNFMVCNF-IHPCNDPISA-N Leu-His-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O LKXANTUNFMVCNF-IHPCNDPISA-N 0.000 description 1
- FAELBUXXFQLUAX-AJNGGQMLSA-N Leu-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C FAELBUXXFQLUAX-AJNGGQMLSA-N 0.000 description 1
- AUNMOHYWTAPQLA-XUXIUFHCSA-N Leu-Met-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AUNMOHYWTAPQLA-XUXIUFHCSA-N 0.000 description 1
- UHNQRAFSEBGZFZ-YESZJQIVSA-N Leu-Phe-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N UHNQRAFSEBGZFZ-YESZJQIVSA-N 0.000 description 1
- CHJKEDSZNSONPS-DCAQKATOSA-N Leu-Pro-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O CHJKEDSZNSONPS-DCAQKATOSA-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
- 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 1
- PPGBXYKMUMHFBF-KATARQTJSA-N Leu-Ser-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PPGBXYKMUMHFBF-KATARQTJSA-N 0.000 description 1
- AIQWYVFNBNNOLU-RHYQMDGZSA-N Leu-Thr-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O AIQWYVFNBNNOLU-RHYQMDGZSA-N 0.000 description 1
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 1
- WSXTWLJHTLRFLW-SRVKXCTJSA-N Lys-Ala-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(O)=O WSXTWLJHTLRFLW-SRVKXCTJSA-N 0.000 description 1
- YKIRNDPUWONXQN-GUBZILKMSA-N Lys-Asn-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YKIRNDPUWONXQN-GUBZILKMSA-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
- XNKDCYABMBBEKN-IUCAKERBSA-N Lys-Gly-Gln Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O XNKDCYABMBBEKN-IUCAKERBSA-N 0.000 description 1
- LCMWVZLBCUVDAZ-IUCAKERBSA-N Lys-Gly-Glu Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CCC([O-])=O LCMWVZLBCUVDAZ-IUCAKERBSA-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
- FHIAJWBDZVHLAH-YUMQZZPRSA-N Lys-Gly-Ser Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FHIAJWBDZVHLAH-YUMQZZPRSA-N 0.000 description 1
- URGPVYGVWLIRGT-DCAQKATOSA-N Lys-Met-Ala Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O URGPVYGVWLIRGT-DCAQKATOSA-N 0.000 description 1
- WQDKIVRHTQYJSN-DCAQKATOSA-N Lys-Ser-Arg Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N WQDKIVRHTQYJSN-DCAQKATOSA-N 0.000 description 1
- IOQWIOPSKJOEKI-SRVKXCTJSA-N Lys-Ser-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IOQWIOPSKJOEKI-SRVKXCTJSA-N 0.000 description 1
- DLCAXBGXGOVUCD-PPCPHDFISA-N Lys-Thr-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DLCAXBGXGOVUCD-PPCPHDFISA-N 0.000 description 1
- CAVRAQIDHUPECU-UVOCVTCTSA-N Lys-Thr-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAVRAQIDHUPECU-UVOCVTCTSA-N 0.000 description 1
- GILLQRYAWOMHED-DCAQKATOSA-N Lys-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCCN GILLQRYAWOMHED-DCAQKATOSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- YLLWCSDBVGZLOW-CIUDSAMLSA-N Met-Gln-Ala Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O YLLWCSDBVGZLOW-CIUDSAMLSA-N 0.000 description 1
- UZWMJZSOXGOVIN-LURJTMIESA-N Met-Gly-Gly Chemical compound CSCC[C@H](N)C(=O)NCC(=O)NCC(O)=O UZWMJZSOXGOVIN-LURJTMIESA-N 0.000 description 1
- RKIIYGUHIQJCBW-SRVKXCTJSA-N Met-His-Glu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O RKIIYGUHIQJCBW-SRVKXCTJSA-N 0.000 description 1
- FWAHLGXNBLWIKB-NAKRPEOUSA-N Met-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCSC FWAHLGXNBLWIKB-NAKRPEOUSA-N 0.000 description 1
- WRXOPYNEKGZWAZ-FXQIFTODSA-N Met-Ser-Cys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(O)=O WRXOPYNEKGZWAZ-FXQIFTODSA-N 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 108010008707 Mucin-1 Proteins 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
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- CDNPIRSCAFMMBE-SRVKXCTJSA-N Phe-Asn-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O CDNPIRSCAFMMBE-SRVKXCTJSA-N 0.000 description 1
- MSHZERMPZKCODG-ACRUOGEOSA-N Phe-Leu-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 MSHZERMPZKCODG-ACRUOGEOSA-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
- IIEOLPMQYRBZCN-SRVKXCTJSA-N Phe-Ser-Cys Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O IIEOLPMQYRBZCN-SRVKXCTJSA-N 0.000 description 1
- BPCLGWHVPVTTFM-QWRGUYRKSA-N Phe-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O BPCLGWHVPVTTFM-QWRGUYRKSA-N 0.000 description 1
- SJRQWEDYTKYHHL-SLFFLAALSA-N Phe-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O SJRQWEDYTKYHHL-SLFFLAALSA-N 0.000 description 1
- XQLBWXHVZVBNJM-FXQIFTODSA-N Pro-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 XQLBWXHVZVBNJM-FXQIFTODSA-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
- 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 1
- WFHYFCWBLSKEMS-KKUMJFAQSA-N Pro-Glu-Phe Chemical compound N([C@@H](CCC(=O)O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C(=O)[C@@H]1CCCN1 WFHYFCWBLSKEMS-KKUMJFAQSA-N 0.000 description 1
- CLNJSLSHKJECME-BQBZGAKWSA-N Pro-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1 CLNJSLSHKJECME-BQBZGAKWSA-N 0.000 description 1
- DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 1
- ZLXKLMHAMDENIO-DCAQKATOSA-N Pro-Lys-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLXKLMHAMDENIO-DCAQKATOSA-N 0.000 description 1
- SMFQZMGHCODUPQ-ULQDDVLXSA-N Pro-Lys-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SMFQZMGHCODUPQ-ULQDDVLXSA-N 0.000 description 1
- ULWBBFKQBDNGOY-RWMBFGLXSA-N Pro-Lys-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@@H]2C(=O)O ULWBBFKQBDNGOY-RWMBFGLXSA-N 0.000 description 1
- 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 1
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- GMJDSFYVTAMIBF-FXQIFTODSA-N Pro-Ser-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GMJDSFYVTAMIBF-FXQIFTODSA-N 0.000 description 1
- SEZGGSHLMROBFX-CIUDSAMLSA-N Pro-Ser-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O SEZGGSHLMROBFX-CIUDSAMLSA-N 0.000 description 1
- PRKWBYCXBBSLSK-GUBZILKMSA-N Pro-Ser-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O PRKWBYCXBBSLSK-GUBZILKMSA-N 0.000 description 1
- WWXNZNWZNZPDIF-SRVKXCTJSA-N Pro-Val-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 WWXNZNWZNZPDIF-SRVKXCTJSA-N 0.000 description 1
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 1
- 102100040120 Prominin-1 Human genes 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- UEJYSALTSUZXFV-SRVKXCTJSA-N Rigin Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O UEJYSALTSUZXFV-SRVKXCTJSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- LVVBAKCGXXUHFO-ZLUOBGJFSA-N Ser-Ala-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O LVVBAKCGXXUHFO-ZLUOBGJFSA-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
- QVOGDCQNGLBNCR-FXQIFTODSA-N Ser-Arg-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O QVOGDCQNGLBNCR-FXQIFTODSA-N 0.000 description 1
- HZWAHWQZPSXNCB-BPUTZDHNSA-N Ser-Arg-Trp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O HZWAHWQZPSXNCB-BPUTZDHNSA-N 0.000 description 1
- 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 1
- FIDMVVBUOCMMJG-CIUDSAMLSA-N Ser-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO FIDMVVBUOCMMJG-CIUDSAMLSA-N 0.000 description 1
- VGNYHOBZJKWRGI-CIUDSAMLSA-N Ser-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO VGNYHOBZJKWRGI-CIUDSAMLSA-N 0.000 description 1
- QPFJSHSJFIYDJZ-GHCJXIJMSA-N Ser-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CO QPFJSHSJFIYDJZ-GHCJXIJMSA-N 0.000 description 1
- 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 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
- OHKFXGKHSJKKAL-NRPADANISA-N Ser-Glu-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OHKFXGKHSJKKAL-NRPADANISA-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
- DJACUBDEDBZKLQ-KBIXCLLPSA-N Ser-Ile-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O DJACUBDEDBZKLQ-KBIXCLLPSA-N 0.000 description 1
- 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 1
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 1
- GZSZPKSBVAOGIE-CIUDSAMLSA-N Ser-Lys-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O GZSZPKSBVAOGIE-CIUDSAMLSA-N 0.000 description 1
- QJKPECIAWNNKIT-KKUMJFAQSA-N Ser-Lys-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QJKPECIAWNNKIT-KKUMJFAQSA-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
- LGIMRDKGABDMBN-DCAQKATOSA-N Ser-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N LGIMRDKGABDMBN-DCAQKATOSA-N 0.000 description 1
- HNDMFDBQXYZSRM-IHRRRGAJSA-N Ser-Val-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O HNDMFDBQXYZSRM-IHRRRGAJSA-N 0.000 description 1
- SIEBDTCABMZCLF-XGEHTFHBSA-N Ser-Val-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SIEBDTCABMZCLF-XGEHTFHBSA-N 0.000 description 1
- 102100035721 Syndecan-1 Human genes 0.000 description 1
- NJEMRSFGDNECGF-GCJQMDKQSA-N Thr-Ala-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O NJEMRSFGDNECGF-GCJQMDKQSA-N 0.000 description 1
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 1
- DGDCHPCRMWEOJR-FQPOAREZSA-N Thr-Ala-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 DGDCHPCRMWEOJR-FQPOAREZSA-N 0.000 description 1
- QGXCWPNQVCYJEL-NUMRIWBASA-N Thr-Asn-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O QGXCWPNQVCYJEL-NUMRIWBASA-N 0.000 description 1
- ASJDFGOPDCVXTG-KATARQTJSA-N Thr-Cys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O ASJDFGOPDCVXTG-KATARQTJSA-N 0.000 description 1
- DSLHSTIUAPKERR-XGEHTFHBSA-N Thr-Cys-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O DSLHSTIUAPKERR-XGEHTFHBSA-N 0.000 description 1
- LAFLAXHTDVNVEL-WDCWCFNPSA-N Thr-Gln-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N)O LAFLAXHTDVNVEL-WDCWCFNPSA-N 0.000 description 1
- LIXBDERDAGNVAV-XKBZYTNZSA-N Thr-Gln-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O LIXBDERDAGNVAV-XKBZYTNZSA-N 0.000 description 1
- NIEWSKWFURSECR-FOHZUACHSA-N Thr-Gly-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O NIEWSKWFURSECR-FOHZUACHSA-N 0.000 description 1
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-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
- FLPZMPOZGYPBEN-PPCPHDFISA-N Thr-Leu-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FLPZMPOZGYPBEN-PPCPHDFISA-N 0.000 description 1
- NCXVJIQMWSGRHY-KXNHARMFSA-N Thr-Leu-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O NCXVJIQMWSGRHY-KXNHARMFSA-N 0.000 description 1
- BDGBHYCAZJPLHX-HJGDQZAQSA-N Thr-Lys-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BDGBHYCAZJPLHX-HJGDQZAQSA-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
- BIBYEFRASCNLAA-CDMKHQONSA-N Thr-Phe-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 BIBYEFRASCNLAA-CDMKHQONSA-N 0.000 description 1
- XHWCDRUPDNSDAZ-XKBZYTNZSA-N Thr-Ser-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N)O XHWCDRUPDNSDAZ-XKBZYTNZSA-N 0.000 description 1
- SGAOHNPSEPVAFP-ZDLURKLDSA-N Thr-Ser-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SGAOHNPSEPVAFP-ZDLURKLDSA-N 0.000 description 1
- AHERARIZBPOMNU-KATARQTJSA-N Thr-Ser-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O AHERARIZBPOMNU-KATARQTJSA-N 0.000 description 1
- BEZTUFWTPVOROW-KJEVXHAQSA-N Thr-Tyr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O BEZTUFWTPVOROW-KJEVXHAQSA-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
- FYBFTPLPAXZBOY-KKHAAJSZSA-N Thr-Val-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O FYBFTPLPAXZBOY-KKHAAJSZSA-N 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- VTHNLRXALGUDBS-BPUTZDHNSA-N Trp-Gln-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N VTHNLRXALGUDBS-BPUTZDHNSA-N 0.000 description 1
- SSSDKJMQMZTMJP-BVSLBCMMSA-N Trp-Tyr-Val Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CC=C(O)C=C1 SSSDKJMQMZTMJP-BVSLBCMMSA-N 0.000 description 1
- UOXPLPBMEPLZBW-WDSOQIARSA-N Trp-Val-Lys Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(O)=O)=CNC2=C1 UOXPLPBMEPLZBW-WDSOQIARSA-N 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- HSVPZJLMPLMPOX-BPNCWPANSA-N Tyr-Arg-Ala Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O HSVPZJLMPLMPOX-BPNCWPANSA-N 0.000 description 1
- QYSBJAUCUKHSLU-JYJNAYRXSA-N Tyr-Arg-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O QYSBJAUCUKHSLU-JYJNAYRXSA-N 0.000 description 1
- GAYLGYUVTDMLKC-UWJYBYFXSA-N Tyr-Asp-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GAYLGYUVTDMLKC-UWJYBYFXSA-N 0.000 description 1
- RYSNTWVRSLCAJZ-RYUDHWBXSA-N Tyr-Gln-Gly Chemical compound OC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RYSNTWVRSLCAJZ-RYUDHWBXSA-N 0.000 description 1
- GZUIDWDVMWZSMI-KKUMJFAQSA-N Tyr-Lys-Cys Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CS)C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GZUIDWDVMWZSMI-KKUMJFAQSA-N 0.000 description 1
- SINRIKQYQJRGDQ-MEYUZBJRSA-N Tyr-Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SINRIKQYQJRGDQ-MEYUZBJRSA-N 0.000 description 1
- XYNFFTNEQDWZNY-ULQDDVLXSA-N Tyr-Met-His Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=C(C=C2)O)N XYNFFTNEQDWZNY-ULQDDVLXSA-N 0.000 description 1
- RWOKVQUCENPXGE-IHRRRGAJSA-N Tyr-Ser-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RWOKVQUCENPXGE-IHRRRGAJSA-N 0.000 description 1
- QFXVAFIHVWXXBJ-AVGNSLFASA-N Tyr-Ser-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O QFXVAFIHVWXXBJ-AVGNSLFASA-N 0.000 description 1
- RIVVDNTUSRVTQT-IRIUXVKKSA-N Tyr-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O RIVVDNTUSRVTQT-IRIUXVKKSA-N 0.000 description 1
- NUQZCPSZHGIYTA-HKUYNNGSSA-N Tyr-Trp-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N NUQZCPSZHGIYTA-HKUYNNGSSA-N 0.000 description 1
- ANHVRCNNGJMJNG-BZSNNMDCSA-N Tyr-Tyr-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CS)C(=O)O)N)O ANHVRCNNGJMJNG-BZSNNMDCSA-N 0.000 description 1
- JFAWZADYPRMRCO-UBHSHLNASA-N Val-Ala-Phe Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JFAWZADYPRMRCO-UBHSHLNASA-N 0.000 description 1
- QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 1
- BMGOFDMKDVVGJG-NHCYSSNCSA-N Val-Asp-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N BMGOFDMKDVVGJG-NHCYSSNCSA-N 0.000 description 1
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 1
- JXGWQYWDUOWQHA-DZKIICNBSA-N Val-Gln-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N JXGWQYWDUOWQHA-DZKIICNBSA-N 0.000 description 1
- XGJLNBNZNMVJRS-NRPADANISA-N Val-Glu-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O XGJLNBNZNMVJRS-NRPADANISA-N 0.000 description 1
- RKIGNDAHUOOIMJ-BQFCYCMXSA-N Val-Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)C(C)C)C(O)=O)=CNC2=C1 RKIGNDAHUOOIMJ-BQFCYCMXSA-N 0.000 description 1
- MDYSKHBSPXUOPV-JSGCOSHPSA-N Val-Gly-Phe Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N MDYSKHBSPXUOPV-JSGCOSHPSA-N 0.000 description 1
- OACSGBOREVRSME-NHCYSSNCSA-N Val-His-Asn Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(N)=O)C(O)=O OACSGBOREVRSME-NHCYSSNCSA-N 0.000 description 1
- XTDDIVQWDXMRJL-IHRRRGAJSA-N Val-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N XTDDIVQWDXMRJL-IHRRRGAJSA-N 0.000 description 1
- HPANGHISDXDUQY-ULQDDVLXSA-N Val-Lys-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N HPANGHISDXDUQY-ULQDDVLXSA-N 0.000 description 1
- SBJCTAZFSZXWSR-AVGNSLFASA-N Val-Met-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N SBJCTAZFSZXWSR-AVGNSLFASA-N 0.000 description 1
- LTTQCQRTSHJPPL-ZKWXMUAHSA-N Val-Ser-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)O)N LTTQCQRTSHJPPL-ZKWXMUAHSA-N 0.000 description 1
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 1
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 1
- NZYNRRGJJVSSTJ-GUBZILKMSA-N Val-Ser-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NZYNRRGJJVSSTJ-GUBZILKMSA-N 0.000 description 1
- BGTDGENDNWGMDQ-KJEVXHAQSA-N Val-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](C(C)C)N)O BGTDGENDNWGMDQ-KJEVXHAQSA-N 0.000 description 1
- ZLNYBMWGPOKSLW-LSJOCFKGSA-N Val-Val-Asp Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLNYBMWGPOKSLW-LSJOCFKGSA-N 0.000 description 1
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 108010005233 alanylglutamic acid Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000002494 anti-cea effect Effects 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
- 108010092854 aspartyllysine Proteins 0.000 description 1
- 108010068265 aspartyltyrosine Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SWEYNHYBJHPVJL-UHFFFAOYSA-N butanoic acid;sodium Chemical compound [Na].CCCC(O)=O SWEYNHYBJHPVJL-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- 108010001064 glycyl-glycyl-glycyl-glycine Proteins 0.000 description 1
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 1
- 108010089804 glycyl-threonine Proteins 0.000 description 1
- 108010010147 glycylglutamine Proteins 0.000 description 1
- 108010037850 glycylvaline Proteins 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 125000001967 indiganyl group Chemical group [H][In]([H])[*] 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 108010044311 leucyl-glycyl-glycine Proteins 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 108010073101 phenylalanylleucine Proteins 0.000 description 1
- 108010083476 phenylalanyltryptophan Proteins 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108010071097 threonyl-lysyl-proline Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 108010080629 tryptophan-leucine Proteins 0.000 description 1
- 108010044292 tryptophyltyrosine Proteins 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 108010003137 tyrosyltyrosine Proteins 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 108010009962 valyltyrosine Proteins 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
Classifications
-
- 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
- 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
- A61K39/46448—Cancer antigens from embryonic or fetal origin
- A61K39/464482—Carcinoembryonic antigen [CEA]
-
- 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
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3007—Carcino-embryonic Antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/50—Colon
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- 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
- 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)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Public Health (AREA)
- Toxicology (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Wood Science & Technology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Reproductive Health (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明涉及生物技术领域,具体涉及一种CEA.CAR‑T及其制备与应用。本发明首先提供一种靶向于癌胚抗原的嵌合抗原受体,所述嵌合抗原受体包括依次连接的结合癌胚抗原(CEA)的多肽、CD28跨摸区(CD28‑TM)、胞内4‑1BB 及胞内CD3ζ。接下来,制备能够表达所述嵌合抗原受体的T细胞,可以特异性识别并杀伤CEA高表达的人肿瘤细胞系及移植瘤模型,证实其是一种安全、特异、有效的CAR‑T细胞,具有重要的临床应用价值。
Description
技术领域
本发明涉及生物技术领域,具体涉及一种CEA.CAR-T及其制备与应用。
背景技术
嵌合抗原受体(Chimeric antigen receptor,CAR)修饰T细胞(CAR-T细胞治疗技术)是近年来发展非常迅速的一种过继免疫细胞治疗技术。通过基因改造技术,效应T细胞的靶向性、杀伤活性和持久性均优于常规应用的免疫细胞,并可克服肿瘤局部免疫抑制微环境和打破宿主免疫耐受状态,是肿瘤免疫细胞治疗领域中新的靶向治疗方式。CAR-T细胞治疗技术的特点在于将抗体的靶向特异性与T细胞的归巢、组织穿透和靶向摧毁能力结合起来用于肿瘤治疗,并在过去的十年中取得了飞速发展,在多种恶性肿瘤的基础研究及临床转化中均取得了显著疗效,多个临床试验结果也令人振奋。
CAR-T技术将能识别某种肿瘤抗原的抗体的抗原结合部与CD3-ζ链或FcεRIγ的胞内部分在体外偶联为一个嵌合蛋白,通过基因转导患者T细胞,使其表达嵌合抗原受体,患者的T细胞被“重编码”后,生成大量肿瘤特异性的CAR-T细。根据胞内区的结构不同,可将CAR-T划分为三代:第一代CAR-T(cFv+信号传导部分)虽然能够介导对肿瘤细胞的杀伤作用,但是不转导增殖信号和诱导细胞因子产生,并且体内持续作用时间不长;第二代CAR-T通过增加共刺激分子(例如CD28)的胞内结构域以延长其体内存活时间,促进其迅速扩增能力,通过构建scFv/Fc/CD28/CD3-ζ的CAR-T可以裂解靶细胞,且不需要B7与CD28的作用,仅靠单一分子就可以传递活化信号,产生大量的IFN-γ、IL-2等细胞因子;第三代CAR-T增加了更多的共刺激信号结构域(通常是肿瘤坏死因子受体家族成员),例如4-1BB(又称CD137)、OX40(又称CD134)、CD27、可诱导共刺激分子(Inducible co-stimulatorymolecule,ICOS)等,第三代CAR-T较第二代具有更好的增强T细胞活化、扩增、抗肿瘤以及促进转基因表达的能。
目前成功运用于临床的CAR-T细胞种类主要包括CD19-CAR-T、HER-2/Neu-CAR-T等,世界范围内多个中心正在进行靶向不同肿瘤相关抗原(Tumor associated antigen,TAA)的CAR-T细胞治疗临床研究,包括靶向CD133、CD138、CD20、CD30、EGFR、c-MET等。目前实体瘤缺乏好的靶点,主要是由于实体瘤细胞的异质性,所以通过大量的临床标本收集和验证,找到更为特异性的实体瘤靶点是当前CAR-T细胞治疗领域的一个重要方向。我们团队先后构建靶向肿瘤抗原CEA、MUC-1等CAR-T细胞,初步建立了CAR-T细胞制备的技术平台,进行了系列临床前研究。
发明内容
鉴于现有技术的情况,本发明的目的在于提供一种靶向于癌胚抗原的嵌合抗原受体及其制备与应用。
为了实现上述目的及其他相关目的,本发明采用如下技术方案:
本发明的第一方面,提供一种靶向于癌胚抗原的嵌合抗原受体,所述嵌合抗原受体包括依次连接的结合癌胚抗原(CEA)的多肽、CD28跨摸区(CD28-TM)、胞内4-1BB及胞内CD3ζ。
优选地,所述结合癌胚抗原的多肽为抗癌胚抗原(CEA)的单链抗体(scFv)。
优选地,所述抗癌胚抗原(CEA)的单链抗体(scFv)包括轻链可变区和重链可变区。
优选地,所述轻链可变区的氨基酸序列如SEQ ID NO.11所示。
优选地,所述重链可变区的氨基酸序列如SEQ ID NO.12所示。
本发明一些实施例中,列举了所述抗癌胚抗原(CEA)的单链抗体(scFv)的氨基酸序列SEQ ID NO.10所示。
优选地,所述CD28跨膜区的氨基酸序列如SEQ ID NO.13所示。
优选地,所述胞内CD3ζ的氨基酸序列如SEQ ID NO.14所示。
优选地,所述胞内4-1BB的氨基酸序列如SEQ ID NO.15所示。
优选地,所述结合癌胚抗原(CEA)的多肽与CD28跨膜区(CD28-TM)之间通过连接片段连接。所述连接片段的氨基酸数量可为≥2个。
优选地,所述连接片段为免疫球蛋白IgD的铰链区片段。进一步优选地,所述连接片段为免疫球蛋白IgG4铰链区片段。
优选地,所述免疫球蛋白IgG4铰链区片段的氨基酸序列如SEQ ID NO.16所示。
所述连接片段可通过二硫键相互连接形成二聚体。
优选地,所述结合癌胚抗原(CEA)的多肽的C末端与所述CD28跨膜区(CD28-TM)的N末端连接。
本发明一些实施例中,列举了所述靶向于癌胚抗原的嵌合抗原受体的氨基酸序列如SEQ ID NO.9所示。
本发明第二方面提供了一种多核苷酸,其编码所述靶向于癌胚抗原的嵌合抗原受体。
本发明第三方面提供了一种表达载体,其含有所述多核苷酸。
本发明第四方面提供了一种宿主细胞,其被所述表达载体所转化。
本发明第五方面,提供一种制备所述靶向于癌胚抗原的嵌合抗原受体的方法,包括步骤:构建含有靶向于癌胚抗原的嵌合抗原受体编码多核苷酸序列的表达载体,然后将所述表达载体转化至宿主细胞中诱导表达,从表达产物中分离获得所述靶向于癌胚抗原的嵌合抗原受体。
本发明的第六方面,提供所述靶向于癌胚抗原的嵌合抗原受体在制备嵌合抗原受体T细胞及肿瘤治疗药物中的用途。
本发明的第七方面,提供一种嵌合抗原受体T细胞,其表达所述靶向于癌胚抗原的嵌合抗原受体。
本发明的第八方面,提供一种肿瘤治疗药物,其含有所述嵌合抗原受体T细胞。
本发明的第九方面,提供一种肿瘤治疗方法,包括步骤:将所述嵌合抗原受体T细胞施用于肿瘤患者。
优选地,所述肿瘤为癌胚抗原高表达的肿瘤。例如:结肠癌、肠癌、胃癌肝转移及胰腺癌。
与现有技术相比,本发明的有益效果为:
肠癌、胃癌肝转移及胰腺癌等恶性实体肿瘤的治疗仍是肿瘤治疗的难点,虽然手术治疗、放化疗、介入治疗等有一定疗效,但患者生存率仍无显著改善。目前,备受关注的CAR-T细胞治疗技术有望成为该类肿瘤治疗的突破口。本发明根据该类肿瘤特异性高表达CEA肿瘤抗原的特点,设计靶向识别CEA的特异性抗体,采用第二代CAR骨架作为载体,设计CEA.CAR-T细胞,并通过一系列体外及体内试验,证实我们自行设计的CEA.CAR-T细胞可以特异性识别并杀伤CEA高表达的人肿瘤细胞系及移植瘤模型,证实其是一种安全、特异、有效的CAR-T细胞,具有重要的临床应用价值。
附图说明
图1:CEA.CAR的结构示意图。
图2:CEA.CAR的整个表达框结构示意图。
图3A:流式结果显示,在IFN-γ刺激前后,LoVo细胞都高表达CEA。
图3B:ELISA结果显示,和其他肿瘤细胞与CART共培养上清相比,LoVo与CEA嵌合CD4+T细胞或CEA嵌合CD8+T细胞共育后IFN-γ分泌最高。
图3C:CEA.CAR-T(BFP+)与LoVo细胞共育后,T细胞活化标记分子(CD69)上调。
图4:LoVo-NSG小鼠模型显示,CEA.CAR-T有效抑制肿瘤生长。
具体实施方式
CAR-T
CAR-T,全称是Chimeric Antigen Receptor T-Cell Immunotherapy,嵌合抗原受体T细胞免疫疗法。
嵌合抗原受体Chimeric Antigen Receptor(CAR)。
以下通过特定的具体实例说明本发明的实施方式,本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用,本说明书中的各项细节也可以基于不同观点与应用,在没有背离本发明的精神下进行各种修饰或改变。
在进一步描述本发明具体实施方式之前,应理解,本发明的保护范围不局限于下述特定的具体实施方案;还应当理解,本发明实施例中使用的术语是为了描述特定的具体实施方案,而不是为了限制本发明的保护范围;在本发明说明书和权利要求书中,除非文中另外明确指出,单数形式“一个”、“一”和“这个”包括复数形式。
当实施例给出数值范围时,应理解,除非本发明另有说明,每个数值范围的两个端点以及两个端点之间任何一个数值均可选用。除非另外定义,本发明中使用的所有技术和科学术语与本技术领域技术人员通常理解的意义相同。除实施例中使用的具体方法、设备、材料外,根据本技术领域的技术人员对现有技术的掌握及本发明的记载,还可以使用与本发明实施例中所述的方法、设备、材料相似或等同的现有技术的任何方法、设备和材料来实现本发明。
除非另外说明,本发明中所公开的实验方法、检测方法、制备方法均采用本技术领域常规的分子生物学、生物化学、染色质结构和分析、分析化学、细胞培养、重组DNA技术及相关领域的常规技术。这些技术在现有文献中已有完善说明,具体可参见Sambrook等MOLECULAR CLONING:A LABORATORY MANUAL,Second edition,Cold Spring HarborLaboratory Press,1989 and Third edition,2001;Ausubel等,CURRENT PROTOCOLS INMOLECULAR BIOLOGY,John Wiley&Sons,New York,1987 and periodic updates;theseries METHODS IN ENZYMOLOGY,Academic Press,San Diego;Wolffe,CHROMATINSTRUCTURE AND FUNCTION,Third edition,Academic Press,San Diego,1998;METHODS INENZYMOLOGY,Vol.304,Chromatin(P.M.Wassarman and A.P.Wolffe,eds.),AcademicPress,San Diego,1999;和METHODS IN MOLECULAR BIOLOGY,Vol.119,ChromatinProtocols(P.B.Becker,ed.)Humana Press,Totowa,1999等。
实施例1靶向于癌胚抗原的嵌合抗原受体表达载体的构建
本发明中,靶向于癌胚抗原的嵌合抗原受体可简称为CEA.CAR。
本发明中,如图1所示,CEA.CAR由依次连接的结合癌胚抗原(CEA)的多肽、CD28跨摸区(CD28-TM)、胞内4-1BB及胞内CD3ζ融合而成。
其中,结合癌胚抗原(CEA)的多肽为抗癌胚抗原(CEA)的单链抗体(scFv)。所述单链抗体包括轻链可变区(VL)和重链可变区(VH)。所述轻链可变区(VL)的编码核苷酸序列如SEQ ID NO.1所示,具体为:
gacacactcctgctatgggtgctgctgctctgggttccaggttccacaggtgacattgtgctgacccaatctccagcttc
tttggctgtgtctcttgggcagagggccaccatgtcctgcagagccggtgaaagtgttgatatttttggcgttgggtttt
tgcactggtaccagcagaaaccaggacagccacccaaactcctcatctatcgtgcatccaacctagaatctgggatccct
gtcaggttcagtggcactgggtctaggacagacttcaccctcatcattgatcctgtggaggctgatgatgttgccaccta
ttactgtcagcaaactaatgaggatccgtacacgttcggaggggggaccaagctggaaataaaa。
所述重链可变区(VH)的编码核苷酸序列如SEQ ID NO.2所示,具体为:
agcagcgaggttcagctacaacagtctggggcagagcttgtggagccaggggcctcagtcaagttgtcctgcacagcttc
tggcttcaacattaaagacacctatatgcactgggtgaagcagaggcctgaacagggcctggaatggattggaaggattg
atcctgcgaatggtaatagtaaatatgtcccgaagttccagggcaaggccactataacagcagacacatcctccaacaca
gcctacctgcagctcaccagcctgacatccgaggacactgccgtctattattgtgctccgtttggttactacgtgtctga
ctatgctatggcctactggggtcaaggaacctcagtcaccgtctcctca。
所述抗癌胚抗原(CEA)的单链抗体(scFv)的编码核苷酸序列如SEQ ID NO.3所示,具体为:
gacacactcctgctatgggtgctgctgctctgggttccaggttccacaggtgacattgtgctgacccaatctccagcttc
tttggctgtgtctcttgggcagagggccaccatgtcctgcagagccggtgaaagtgttgatatttttggcgttgggtttt
tgcactggtaccagcagaaaccaggacagccacccaaactcctcatctatcgtgcatccaacctagaatctgggatccct
gtcaggttcagtggcactgggtctaggacagacttcaccctcatcattgatcctgtggaggctgatgatgttgccaccta
ttactgtcagcaaactaatgaggatccgtacacgttcggaggggggaccaagctggaaataaaaggcagtactagcggcg
gtggctccgggggcggttccggtgggggcggcagcagcgaggttcagctacaacagtctggggcagagcttgtggagcca
ggggcctcagtcaagttgtcctgcacagcttctggcttcaacattaaagacacctatatgcactgggtgaagcagaggcc
tgaacagggcctggaatggattggaaggattgatcctgcgaatggtaatagtaaatatgtcccgaagttccagggcaagg
ccactataacagcagacacatcctccaacacagcctacctgcagctcaccagcctgacatccgaggacactgccgtctat
tattgtgctccgtttggttactacgtgtctgactatgctatggcctactggggtcaaggaacctcagtcaccgtctcctca。
CD28跨膜区(CD28-TM)的编码核苷酸序列如SEQ ID NO.4所示,具体为:Atgttctgggtgctggtggtggtgggcggggtgctggcctgctacagcctgctggtgacagtggccttcatcatcttttgggtg。
胞内4-1BB的编码核苷酸序列如SEQ ID NO.5所示,具体为:
CGTTTCTCTGTTGTTAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTG。
胞内CD3ζ的编码核苷酸序列如SEQ ID NO.6所示,具体为:
cgggtgaagttcagcagaagcgccgacgcccctgcctaccagcagggccagaatcagctgtacaacgagctgaacctgggcagaagggaagagtacgacgtcctggataagcggagaggccgggaccctgagatgggcggcaagcctcggcggaagaacccccaggaaggcctgtataacgaactgcAgaaagacaagatggccgaggcctacagcgagatcggcatgaagggcgagcggaggcggggcaagggccacgacggcctgtatcagggcctgtccaccgccaccaaggatacctacgacgccctgcacatgcaggccctgcccccaagg。
结合癌胚抗原(CEA)的多肽、CD28跨摸区(CD28-TM)之间免疫球蛋白IgG4铰链区片段作为连接片段连接。所述免疫球蛋白IgG4铰链区片段的编码核苷酸序列如SEQ ID NO.7所示,具体为:
Gagagcaagtacggccctccctgccccccttgccctgcccccgagttcctgggcggacccagcgtgttcctgttcccccccaagcccaaggacaccctgatgatcagccggacccccgaggtgacctgcgtggtggtggacgtgagccaggaagatcccgaggtccagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttcaacagcacctaccgggtggtgtctgtgctgaccgtgctgcaccaggactggctgaacggcaaagaatacaagtgcaaggtgtccaacaagggcctgcccagcagcatcgaaaagaccatcagcaaggccaagggccagcctcgcgagccccaggtgtacaccctgcctccctcccaggaagagatgaccaagaaccaggtgtccctgacctgcctggtgaagggcttctaccccagcgacatcgccgtggagtgggagagcaacggccagcctgagaacaactacaagaccacccctcccgtgctggacagcgacggcagcttcttcctgtacagccggctgaccgtggacaagagccggtggcaggaaggcaacgtctttagctgcagcgtgatgcacgaggccctgcacaaccactacacccagaagagcctgagcctgtccctgggcaag。
为了便于对CEA.CAR的识别,在胞内CD3ζ的C端连接了t2A-Tag BFP。
委托公司合成CEA.CAR的整个表达框,如图2所示,插入pCART-EF1a-ScFv-car框载体(购自上海吉凯公司),经测序正确后,使用Qiagen公司的质粒纯化试剂盒提取并纯化质粒,获得重组表达载体的高品质质粒。
经测序可知,CEA.CAR的全长基因序列正确,均与预期相符。
具体地,CEA.CAR的编码核苷酸序列如SEQ ID NO.8所示,具体为:
atggagacagacacactcctgctatgggtgctgctgctctgggttccaggttccacaggTgacacactcctgctatgggtgctgctgctctgggttccaggttccacaggtgacattgtgctgacccaatctccagcttctttggctgtgtctcttgggcagagggccaccatgtcctgcagagccggtgaaagtgttgatatttttggcgttgggtttttgcactggtaccagcagaaaccaggacagccacccaaactcctcatctatcgtgcatccaacctagaatctgggatccctgtcaggttcagtggcactgggtctaggacagacttcaccctcatcattgatcctgtggaggctgatgatgttgccacctattactgtcagcaaactaatgaggatccgtacacgttcggaggggggaccaagctggaaataaaaggcagtactagcggcggtggctccgggggcggttccggtgggggcggcagcagcgaggttcagctacaacagtctggggcagagcttgtggagccaggggcctcagtcaagttgtcctgcacagcttctggcttcaacattaaagacacctatatgcactgggtgaagcagaggcctgaacagggcctggaatggattggaaggattgatcctgcgaatggtaatagtaaatatgtcccgaagttccagggcaaggccactataacagcagacacatcctccaacacagcctacctgcagctcaccagcctgacatccgaggacactgccgtctattattgtgctccgtttggttactacgtgtctgactatgctatggcctactggggtcaaggaacctcagtcaccgtctcctcaGagagcaagtacggccctccctgccccccttgccctgcccccgagttcctgggcggacccagcgtgttcctgttcccccccaagcccaaggacaccctgatgatcagccggacccccgaggtgacctgcgtggtggtggacgtgagccaggaagatcccgaggtccagttcaattggtacgtggacggcgtggaagtgcacaacgccaagaccaagcccagagaggaacagttcaacagcacctaccgggtggtgtctgtgctgaccgtgctgcaccaggactggctgaacggcaaagaatacaagtgcaaggtgtccaacaagggcctgcccagcagcatcgaaaagaccatcagcaaggccaagggccagcctcgcgagccccaggtgtacaccctgcctccctcccaggaagagatgaccaagaaccaggtgtccctgacctgcctggtgaagggcttctaccccagcgacatcgccgtggagtgggagagcaacggccagcctgagaacaactacaagaccacccctcccgtgctggacagcgacggcagcttcttcctgtacagccggctgaccgtggacaagagccggtggcaggaaggcaacgtctttagctgcagcgtgatgcacgaggccctgcacaaccactacacccagaagagcctgagcctgtccctgggcaagAtgttctgggtgctggtggtggtgggcggggtgctggcctgctacagcctgctggtgacagtggccttcatcatcttttgggtgCGTTTCTCTGTTGTTAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCAGTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGAGGATGTGAACTGcgggtgaagttcagcagaagcgccgacgcccctgcctaccagcagggccagaatcagctgtacaacgagctgaacctgggcagaagggaagagtacgacgtcctggataagcggagaggccgggaccctgagatgggcggcaagcctcggcggaagaacccccaggaaggcctgtataacgaactgcAgaaagacaagatggccgaggcctacagcgagatcggcatgaagggcgagcggaggcggggcaagggccacgacggcctgtatcagggcctgtccaccgccaccaaggatacctacgacgccctgcacatgcaggccctgcccccaagg。
采用现有技术,对重组表达载体的高品质质粒转至宿主细胞中诱导表达,从表达产物中分离纯化获得CEA.CAR。对获得的CEA.CAR经N/C末端序列分析,结果表明所表达的CEA.CAR均读框无误,与理论N/C末端氨基酸序列一致。
因此,可得知,CEA.CAR的氨基酸序列如SEQ ID NO.9所示,具体为:_
METDTLLLWVLLLWVPGSTGDTLLLWVLLLWVPGSTGDIVLTQSPASLAVS
LGQRATMSCRAGESVDIFGVGFLHWYQQKPGQPPKLLIYRASNLESGIPVRFSG
TGSRTDFTLIIDPVEADDVATYYCQQTNEDPYTFGGGTKLEIKGSTSGGGSGGG
SGGGGSSEVQLQQSGAELVEPGASVKLSCTASGFNIKDTYMHWVKQRPEQGLEW
IGRIDPANGNSKYVPKFQGKATITADTSSNTAYLQLTSLTSEDTAVYYCAPFGY
YVSDYAMAYWGQGTSVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLM
ISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVL
TVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK
SRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKMFWVLVVVGGVLACYSLLVTV
AFIIFWVRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL
RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNP
QEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQA
LPPRL。
抗癌胚抗原(CEA)的单链抗体(scFv)的氨基酸序列如SEQ ID NO.10所示,具体为:
DTLLLWVLLLWVPGSTGDIVLTQSPASLAVSLGQRATMSCRAGESVDIFGVGFLHWYQQKPGQPPKLLIYRASNLESGIPVRFSGTGSRTDFTLIIDPVEADDVATYYCQQTNEDPYTFGGGTKLEIKGSTSGGGSGGGSGGGGSSEVQLQQSGAELVEPGASVKLSCTASGFNIKDTYMHWVKQRPEQGLEWIGRIDPANGNSKYVPKFQGKATITADTSSNTAYLQLTSLTSEDTAVYYCAPFGYYVSDYAMAYWGQGTSVTVSS。
抗癌胚抗原(CEA)的单链抗体(scFv)的轻链可变区的氨基酸序列如SEQ ID NO.11所示,具体为:
DTLLLWVLLLWVPGSTGDIVLTQSPASLAVSLGQRATMSCRAGESVDIFGVGFLHWYQQKPGQPPKLLIYRASNLESGIPVRFSGTGSRTDFTLIIDPVEADDVATYYCQQTNEDPYTFGGGTKLEIK。
抗癌胚抗原(CEA)的单链抗体(scFv)的重链可变区的氨基酸序列如SEQ ID NO.12所示,具体为:
SSEVQLQQSGAELVEPGASVKLSCTASGFNIKDTYMHWVKQRPEQGLEWIGRIDPANGNSKYVPKFQGKATITADTSSNTAYLQLTSLTSEDTAVYYCAPFGYYVSDYAMAYWGQGTSVTVSS。
CD28跨膜区(CD28-TM)的氨基酸序列如SEQ ID NO.13所示,具体为:
MFWVLVVVGGVLACYSLLVTVAFIIFWV。
胞内4-1BB的氨基酸序列如SEQ ID NO.14所示,具体为:
RFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL。
胞内CD3ζ的氨基酸序列如SEQ ID NO.15所示,具体为:
RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR。
结合癌胚抗原(CEA)的多肽、CD28跨膜区(CD28-TM)之间免疫球蛋白IgG4铰链区片段作为连接片段连接。所述免疫球蛋白IgG4铰链区片段的氨基酸序列如SEQ ID NO.16所示,具体为:
ESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK。
实施例2靶向于癌胚抗原的嵌合抗原受体表达慢病毒制备
一、制备慢病毒
1.目的:介绍生产和浓缩用于后续哺乳动物细胞转导的慢病毒的方法。
2.设备和材料
试剂及材料 | 公司 | 货号 |
DMEM*培养基 | Gibco | 11960044 |
RPMI培养基 | Lonza | 12-115Q |
热灭活FBS§ | Gibco | 16140 |
CalPhos哺乳动物细胞转染试剂盒 | ClonTech | 631312 |
丁酸钠 | Sigma | B5887-5G |
聚乙二醇(PEG) | Sigma | P5413-1KG |
*DMEM“完全”培养基为加入10%热灭活FBS的DMEM培养基。在Silver Lab中,我们还添加了100U/ml青霉素-链霉素。
§若无热灭活FBS,可将常规FBS置于56℃水浴30分钟,完全解冻以热灭活FBS。
3.步骤
注意事项:传统的病毒制备需要8个10厘米培养皿。可根据需要进行调整。此过程中,同时制备3种病毒,每种病毒需要8个10厘米培养皿。
3.1准备HEK 293T:
3.1.1.准备制备慢病毒时,提前3天将HEK 293T细胞传代接种于T-150培养瓶中。HEK 293T细胞培养方法如下(注意:尽量缩短细胞在浓缩胰蛋白酶中和培养箱外面的时间):
3.1.1.1.将培养瓶中的培养基吸净,弃掉。
3.1.1.2.向每个T-150培养瓶中加入2ml 0.25%胰蛋白酶,并倾斜培养瓶以确保胰蛋白酶覆盖整个瓶底。
3.1.1.3. 37℃孵育2-3分钟。
3.1.1.4.检查细胞是否已从瓶底脱落;可倾斜培养瓶以促进细胞消化脱落。
3.1.1.5.待细胞消化脱落后,向每个培养瓶中加入10ml DMEM完全培养基,并用移液管充分混合,以确保细胞完全悬浮于溶液中。
3.1.1.6.将10μl细胞悬浮液转移至600μl离心管中,并加入90μl培养基稀释、混匀。
3.1.1.7.从上述1:10稀释过的细胞悬液中取出15μl并与15μl台盼蓝混合,计数并计算出细胞密度。
3.1.1.8.以5×106个/20ml培养基的细胞密度将细胞接种于T-150培养瓶中(3天后每个T-150培养瓶中的细胞数量可达到45-60×106)。
3.1.1.9.将培养瓶平放于的CO2培养箱中。
3.1.2.培养72小时后,观察细胞生长情况,若细胞密度达到80-90%,细胞状态良好(细胞明亮,紧密附着于瓶底,细胞边缘平整等)。则可用于后续慢病毒制备。
3.2.慢病毒制备的第1天:
注意:由于需要先等细胞粘附于培养皿底部才可开始进行CalPhos转染,而这一过程大概需要需要4-6小时。因此要在慢病毒制备的第1天尽早将细胞接种于10cm培养皿中。
注意:或者,可在转染前24小时按照3.5×10 6个/9ml密度接种于10cm培养皿中。
3.2.1.制备一种慢病毒,需要8个10cm细胞培养皿,并标明日期、姓名和质粒ID号。
3.2.2.如3.1.1.1-3.1.1.7所述,将HEK 293T细胞用胰蛋白酶消化,DMEM完全培养基终止消化并计数。
3.2.3.确定慢病毒制备所需的细胞数量:7×106个细胞/皿,8个皿/病毒。
3.2.4.实际收取的细胞要比以上所需细胞数量多3.5×106个,以防损耗(例如,制备2种病毒需实际收取171.5×106,每种病毒8个培养皿的细胞)。
3.2.5.加入适量的培养基使最终浓度为7×106个细胞/9ml。
3.2.6.将9ml细胞悬浮液等分到每个标记好的10cm培养皿中。
3.2.7.将每个培养皿平放于生物安全柜上,沿前后左右轻轻地来回移动,以使细胞均匀铺于皿底。
3.2.8.将培养皿放回培养箱。勿将多个培养瓶罗放于培养箱中。由于细胞的生长状况不同,细胞密度达到80%大概需要3-6个小时。之后,便可开始进行CalPhos转染。
3.2.9.按下表计算所需的试剂体积。
试剂 | 每个培养皿需要的量 |
构建的质粒DNA | 15μg |
病毒载体PCMV-Rev2(pS013) | 1μg |
病毒载体PCHGP-2(pS014) | 10μg |
病毒载体PCMV-G(pS015) | 2μg |
2M CaCl2 | 62μl |
无菌水 | 总体积为500μl |
3.2.10.按照以下顺序将无菌水(来自CalPhos转染试剂盒),质粒DNA和2M CaCl 2溶液(来自CalPhos转染试剂盒)加入15ml离心管中,并充分混合。
3.2.11.按照平均每个反应体系500μl 2X HBS,将适量的2X HBS加入50ml离心管中,适当增加体积,避免损耗(例如,8个培养皿反应体系可共加4100μl HBS)。
3.2.12.使用1ml移液枪,将等体积的DNA/CaCl2混合物逐滴加入HBS中,滴加的同时轻轻晃动HBS管。
3.2.13.将混合物在室温下孵育20分钟。待孵育即将结束时,取出早上铺好的293T细胞。
3.2.14.用1ml移液枪上下吹打混合HBS/CaCl2/DNA溶液。
3.2.15.将1ml溶液逐滴滴加到每个培养皿中。
3.2.16.重复步骤3.2.7,充分混匀。
3.2.17.处理完所有培养皿后,将培养皿放入培养箱过夜孵育,不超过18小时即可进行下一步实验。
3.3.慢病毒制备的第2天(取出CalPhos成分)
3.3.1.按照如下操作准备0.6M丁酸钠溶液:
3.3.1.1.将3.3027g丁酸钠(Sigma,货号B5887-5G)溶于50ml H2O中。0.22-μm真空过滤器灭菌。室温储存。
3.3.2.除去CalPhos成分(对细胞有毒),并在转染后18小时内更换培养基。
3.3.2.1.配制第2天所需培养基:245ml DMEM完全培养基中加入2.45ml 0.6M丁酸钠。(注意:本实验中共24个培养皿,每个培养皿中加入10ml培养基,可适当调整。)
3.3.2.2.将上述培养基及不含镁、钙的1X PBS预热至37℃。
3.3.2.3.为避免细胞在培养箱外面呆的时间过长,可一次性取出两块培养皿依次进行处理。
3.3.2.4.在培养皿的中央标记一条线来区分移除和加入培养基的部位,以减少对其他部位细胞的伤害。
3.3.2.6.用10ml移液管和移液器放置缓慢,轻轻吸除培养基。
3.3.2.7.旋转培养皿,将吸除培养基的位置转到对侧,用10ml移液管沿培养皿的上缘缘缓慢加入5ml上述预热的PBS。使培养基可沿培养皿底面缓缓流下。
3.3.2.8.沿前后左右来回移动培养皿(如步骤3.2.7所示)以彻底冲洗。然后旋转培养皿,在吸除培养基的位置吸除PBS洗涤液。
3.3.2.9.缓缓加入10ml步骤3.3.2.1中制备的含有丁酸钠的DMEM完全培养基。
3.3.2.10.将培养皿回培养箱。
3.3.2.11.按照步骤3.3.2.3-3.3.2.9处理其余的培养皿。
3.4生产慢病毒的第三天(一代收集和PEG处理)
3.4.1收集病毒上清(24小时后换液)
3.5病毒重悬
3.5.8.1将收集到的病毒每盘加入50μ无血清的1640。不要用移液管上下混匀。
3.5.8.2将超净管用封口膜封口,在振荡器上震动若干秒将其完全重悬。
3.5.8.3将其在4摄氏度环境中静置30min-1h,每份病毒在其V底冷冻管上做标记。
3.5.8.4将病毒悬液在振荡器上震荡混匀至没有明显团块。(超速离心后溶液及时没有明显沉淀也是浓稠的)。
3.5.8.5将同一种病毒的重悬液加在同一个管子中。
3.5.8.6将空的超净管放入50ml离心管中,震动15sec将参与病毒上清移到管底。
3.5.8.7将3.4.4.5中的上清转移到一个总收集管中。
3.5.8.8将上清震荡使其均匀。
3.5.8.9将一份上清转移到V底冻存管中(每份大约25-50μl)。
3.5.9将每份病毒贮存于-80℃。
二、慢病毒滴定
1.目的:介绍评估慢病毒转导效率的方法
2.设备和材料
*DMEM“完全”培养基为加入10%热灭活FBS的DMEM培养基。在Silver Lab中,我们还添加了100U/ml青霉素-链霉素。
§若无热灭活FBS,可将常规FBS置于56℃水浴30分钟,完全解冻以热灭活FBS。
3.步骤
第1天
注意:以最高病毒输入量额外转染几个孔用于长期培养和冷冻保存
注意:空载体转导的细胞作阴性对照
1.每孔用0.5ml RPMI完全培养基将0.1×106个Jurkat细胞接种至24孔板中。
2.每孔按照1:1000加入聚凝胺(4mg/ml)(例如0.5ml培养基中加入0.5μl 4ml/ml的聚凝胺)。
3.复苏病毒
4.用RPMI完全培养基,1:1000稀释浓缩病毒。
5.以下列浓度将病毒加入每个孔中。
a.加入50ul 1:1000稀释的病毒(最终的病毒体积:5×10-5ml)
b.加入0.5ul未稀释病毒(最终的病毒体积:5×10-4ml)
c.加入1ul未稀释的病毒(最终的病毒体积:为1×10-3ml)
d.加入5ul未稀释的病毒(最终的病毒体积:5×10-3ml)
6.37℃过夜孵育。
第2天
每个孔中加入0.5ml新鲜的RPMI完全培养基以稀释聚凝胺。
第3天
1.收集样品并利用流式细胞术进行检测以分析基因的表达。
2.以最高病毒输入量额外转染几个孔用于长期培养和冷冻保存
滴度计算:
注意:滴度计算的线性范围是15%-45%载体表达率。
最终,经计算获得靶向于癌胚抗原的嵌合抗原受体表达慢病毒的滴度符合要求。
实施例3T细胞的体外培养、遗传修饰和扩增
采用实施例2制备的靶向于癌胚抗原的嵌合抗原受体表达慢病毒慢病毒转导人T淋巴细胞:
1.将PBMC接种于24孔板的3个孔中,每孔500万个细胞,1ml RPMI。
2.每孔加入1ug/ml OKT3和1:1000稀释的IL2刺激细胞。
3. 37℃孵育24h。
4. 6ml病毒上清液中加入6ul聚凝胺(4mg/ml),混匀。
5.每孔加入2ml病毒/聚凝胺混合物。
6. 1800r/s,离心50分钟。
7.每孔吸除2/3上清液;并向每个孔中加入2ml病毒/聚凝胺混合物和1:1000稀释的IL2。
8.37℃孵育过夜。
9.吸除2/3上清液;并向每个孔中加入2ml新鲜RPMI和1:1000稀释的IL2。
10. 37℃孵育过夜。
11.收集样品并利用流式细胞术进行检测(CD4,CD8,TIM3)以分析目的基因表达情况。
从中筛选出成功进行了遗传修饰的T细胞,亦即CEA.CAR-T。
接下来CEA高表达细胞株LoVo的鉴定及与CEA-CAR-T共培养,观察CEA-CAR-T细胞效应功能的变化:
图3A.在IFN-γ刺激或不刺激的情况下,FACS检测结果显示与293T、HT-29、CaCO2和A375相比,LoVo细胞中CEA呈高表达。
图3B.与293T,HT-29,CaCO2和A375组相比,CEA.CAR-T与LoVo共培养时,CD4和CD8亚群中IFN-γ产生显著增加。
图3C.构建并浓缩高滴度复制缺陷型慢病毒载体。在转染前24小时,将11-12×106的293T人胚胎肾细胞用10cm培养板铺板。慢病毒载体纯化后采用脂质体法转染293T细胞,转染24和48小时后收集培养上清。采用转染CEA.CAR的Jurkat与LoVo进行共培养杀伤实验,结果表明共培养8h后,Jurkat细胞中CD69分子表达水平显著上调。
实施例4体内试验验证CEA.CAR-T细胞的抗肿瘤作用
选用实施例3中所构建的CEA.CAR-T细胞,采用人肠癌细胞株LoVo在NSG小鼠中构建移植瘤模型,体内试验探讨CEA.CAR-T在肠癌模型治疗中的作用。
如图4所示,6只NSG小鼠皮下接种5x106人肠癌细胞株LoVo,3只小鼠在第14天接种6x106的CEA.CAR-T细胞,3只小鼠在第14天接种Pbs,每2天测量肿瘤大小。LoVo-NSG小鼠模型显示,CEA CART有效抑制肿瘤生长。
本发明还尝试过将CEA.CAR上的抗CEA的抗体替换成针对该抗原的抗体,来制备其他CAR-T,结果各方面的效果没有本发明的CEA.CAR-T效果好。
以上的实施例是为了说明本发明公开的实施方案,并不能理解为对本发明的限制。此外,本文所列出的各种修改以及发明中方法、组合物的变化,在不脱离本发明的范围和精神的前提下对本领域内的技术人员来说是显而易见的。虽然已结合本发明的多种具体优选实施例对本发明进行了具体的描述,但应当理解,本发明不应仅限于这些具体实施例。事实上,各种如上所述的对本领域内的技术人员来说显而易见的修改来获取发明都应包括在本发明的范围内。
SEQUENCE LISTING
<110> 常州市第一人民医院
<120> CEA.CAR-T及其制备与应用
<130> 171719
<160> 16
<170> PatentIn version 3.3
<210> 1
<211> 384
<212> DNA
<213> Artificial
<220>
<223> 轻链可变区(VL)的编码核苷酸序列
<400> 1
gacacactcc tgctatgggt gctgctgctc tgggttccag gttccacagg tgacattgtg 60
ctgacccaat ctccagcttc tttggctgtg tctcttgggc agagggccac catgtcctgc 120
agagccggtg aaagtgttga tatttttggc gttgggtttt tgcactggta ccagcagaaa 180
ccaggacagc cacccaaact cctcatctat cgtgcatcca acctagaatc tgggatccct 240
gtcaggttca gtggcactgg gtctaggaca gacttcaccc tcatcattga tcctgtggag 300
gctgatgatg ttgccaccta ttactgtcag caaactaatg aggatccgta cacgttcgga 360
ggggggacca agctggaaat aaaa 384
<210> 2
<211> 369
<212> DNA
<213> Artificial
<220>
<223> 重链可变区(VH)的编码核苷酸序列
<400> 2
agcagcgagg ttcagctaca acagtctggg gcagagcttg tggagccagg ggcctcagtc 60
aagttgtcct gcacagcttc tggcttcaac attaaagaca cctatatgca ctgggtgaag 120
cagaggcctg aacagggcct ggaatggatt ggaaggattg atcctgcgaa tggtaatagt 180
aaatatgtcc cgaagttcca gggcaaggcc actataacag cagacacatc ctccaacaca 240
gcctacctgc agctcaccag cctgacatcc gaggacactg ccgtctatta ttgtgctccg 300
tttggttact acgtgtctga ctatgctatg gcctactggg gtcaaggaac ctcagtcacc 360
gtctcctca 369
<210> 3
<211> 801
<212> DNA
<213> Artificial
<220>
<223> 抗癌胚抗原(CEA)的单链抗体(scFv)的编码核苷酸序列
<400> 3
gacacactcc tgctatgggt gctgctgctc tgggttccag gttccacagg tgacattgtg 60
ctgacccaat ctccagcttc tttggctgtg tctcttgggc agagggccac catgtcctgc 120
agagccggtg aaagtgttga tatttttggc gttgggtttt tgcactggta ccagcagaaa 180
ccaggacagc cacccaaact cctcatctat cgtgcatcca acctagaatc tgggatccct 240
gtcaggttca gtggcactgg gtctaggaca gacttcaccc tcatcattga tcctgtggag 300
gctgatgatg ttgccaccta ttactgtcag caaactaatg aggatccgta cacgttcgga 360
ggggggacca agctggaaat aaaaggcagt actagcggcg gtggctccgg gggcggttcc 420
ggtgggggcg gcagcagcga ggttcagcta caacagtctg gggcagagct tgtggagcca 480
ggggcctcag tcaagttgtc ctgcacagct tctggcttca acattaaaga cacctatatg 540
cactgggtga agcagaggcc tgaacagggc ctggaatgga ttggaaggat tgatcctgcg 600
aatggtaata gtaaatatgt cccgaagttc cagggcaagg ccactataac agcagacaca 660
tcctccaaca cagcctacct gcagctcacc agcctgacat ccgaggacac tgccgtctat 720
tattgtgctc cgtttggtta ctacgtgtct gactatgcta tggcctactg gggtcaagga 780
acctcagtca ccgtctcctc a 801
<210> 4
<211> 84
<212> DNA
<213> Artificial
<220>
<223> CD28跨膜区(CD28-TM)的编码核苷酸序列
<400> 4
atgttctggg tgctggtggt ggtgggcggg gtgctggcct gctacagcct gctggtgaca 60
gtggccttca tcatcttttg ggtg 84
<210> 5
<211> 141
<212> DNA
<213> Artificial
<220>
<223> 胞内4-1BB的编码核苷酸序列
<400> 5
cgtttctctg ttgttaaacg gggcagaaag aaactcctgt atatattcaa acaaccattt 60
atgagaccag tacaaactac tcaagaggaa gatggctgta gctgccgatt tccagaagaa 120
gaagaaggag gatgtgaact g 141
<210> 6
<211> 336
<212> DNA
<213> Artificial
<220>
<223> 胞内CD3ζ的编码核苷酸序列
<400> 6
cgggtgaagt tcagcagaag cgccgacgcc cctgcctacc agcagggcca gaatcagctg 60
tacaacgagc tgaacctggg cagaagggaa gagtacgacg tcctggataa gcggagaggc 120
cgggaccctg agatgggcgg caagcctcgg cggaagaacc cccaggaagg cctgtataac 180
gaactgcaga aagacaagat ggccgaggcc tacagcgaga tcggcatgaa gggcgagcgg 240
aggcggggca agggccacga cggcctgtat cagggcctgt ccaccgccac caaggatacc 300
tacgacgccc tgcacatgca ggccctgccc ccaagg 336
<210> 7
<211> 687
<212> DNA
<213> Artificial
<220>
<223> 免疫球蛋白IgG4铰链区片段的编码核苷酸序列
<400> 7
gagagcaagt acggccctcc ctgcccccct tgccctgccc ccgagttcct gggcggaccc 60
agcgtgttcc tgttcccccc caagcccaag gacaccctga tgatcagccg gacccccgag 120
gtgacctgcg tggtggtgga cgtgagccag gaagatcccg aggtccagtt caattggtac 180
gtggacggcg tggaagtgca caacgccaag accaagccca gagaggaaca gttcaacagc 240
acctaccggg tggtgtctgt gctgaccgtg ctgcaccagg actggctgaa cggcaaagaa 300
tacaagtgca aggtgtccaa caagggcctg cccagcagca tcgaaaagac catcagcaag 360
gccaagggcc agcctcgcga gccccaggtg tacaccctgc ctccctccca ggaagagatg 420
accaagaacc aggtgtccct gacctgcctg gtgaagggct tctaccccag cgacatcgcc 480
gtggagtggg agagcaacgg ccagcctgag aacaactaca agaccacccc tcccgtgctg 540
gacagcgacg gcagcttctt cctgtacagc cggctgaccg tggacaagag ccggtggcag 600
gaaggcaacg tctttagctg cagcgtgatg cacgaggccc tgcacaacca ctacacccag 660
aagagcctga gcctgtccct gggcaag 687
<210> 8
<211> 2109
<212> DNA
<213> Artificial
<220>
<223> CEA.CAR的编码核苷酸序列
<400> 8
atggagacag acacactcct gctatgggtg ctgctgctct gggttccagg ttccacaggt 60
gacacactcc tgctatgggt gctgctgctc tgggttccag gttccacagg tgacattgtg 120
ctgacccaat ctccagcttc tttggctgtg tctcttgggc agagggccac catgtcctgc 180
agagccggtg aaagtgttga tatttttggc gttgggtttt tgcactggta ccagcagaaa 240
ccaggacagc cacccaaact cctcatctat cgtgcatcca acctagaatc tgggatccct 300
gtcaggttca gtggcactgg gtctaggaca gacttcaccc tcatcattga tcctgtggag 360
gctgatgatg ttgccaccta ttactgtcag caaactaatg aggatccgta cacgttcgga 420
ggggggacca agctggaaat aaaaggcagt actagcggcg gtggctccgg gggcggttcc 480
ggtgggggcg gcagcagcga ggttcagcta caacagtctg gggcagagct tgtggagcca 540
ggggcctcag tcaagttgtc ctgcacagct tctggcttca acattaaaga cacctatatg 600
cactgggtga agcagaggcc tgaacagggc ctggaatgga ttggaaggat tgatcctgcg 660
aatggtaata gtaaatatgt cccgaagttc cagggcaagg ccactataac agcagacaca 720
tcctccaaca cagcctacct gcagctcacc agcctgacat ccgaggacac tgccgtctat 780
tattgtgctc cgtttggtta ctacgtgtct gactatgcta tggcctactg gggtcaagga 840
acctcagtca ccgtctcctc agagagcaag tacggccctc cctgcccccc ttgccctgcc 900
cccgagttcc tgggcggacc cagcgtgttc ctgttccccc ccaagcccaa ggacaccctg 960
atgatcagcc ggacccccga ggtgacctgc gtggtggtgg acgtgagcca ggaagatccc 1020
gaggtccagt tcaattggta cgtggacggc gtggaagtgc acaacgccaa gaccaagccc 1080
agagaggaac agttcaacag cacctaccgg gtggtgtctg tgctgaccgt gctgcaccag 1140
gactggctga acggcaaaga atacaagtgc aaggtgtcca acaagggcct gcccagcagc 1200
atcgaaaaga ccatcagcaa ggccaagggc cagcctcgcg agccccaggt gtacaccctg 1260
cctccctccc aggaagagat gaccaagaac caggtgtccc tgacctgcct ggtgaagggc 1320
ttctacccca gcgacatcgc cgtggagtgg gagagcaacg gccagcctga gaacaactac 1380
aagaccaccc ctcccgtgct ggacagcgac ggcagcttct tcctgtacag ccggctgacc 1440
gtggacaaga gccggtggca ggaaggcaac gtctttagct gcagcgtgat gcacgaggcc 1500
ctgcacaacc actacaccca gaagagcctg agcctgtccc tgggcaagat gttctgggtg 1560
ctggtggtgg tgggcggggt gctggcctgc tacagcctgc tggtgacagt ggccttcatc 1620
atcttttggg tgcgtttctc tgttgttaaa cggggcagaa agaaactcct gtatatattc 1680
aaacaaccat ttatgagacc agtacaaact actcaagagg aagatggctg tagctgccga 1740
tttccagaag aagaagaagg aggatgtgaa ctgcgggtga agttcagcag aagcgccgac 1800
gcccctgcct accagcaggg ccagaatcag ctgtacaacg agctgaacct gggcagaagg 1860
gaagagtacg acgtcctgga taagcggaga ggccgggacc ctgagatggg cggcaagcct 1920
cggcggaaga acccccagga aggcctgtat aacgaactgc agaaagacaa gatggccgag 1980
gcctacagcg agatcggcat gaagggcgag cggaggcggg gcaagggcca cgacggcctg 2040
tatcagggcc tgtccaccgc caccaaggat acctacgacg ccctgcacat gcaggccctg 2100
cccccaagg 2109
<210> 9
<211> 704
<212> PRT
<213> Artificial
<220>
<223> CEA.CAR的氨基酸序列
<400> 9
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val
20 25 30
Pro Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu
35 40 45
Ala Val Ser Leu Gly Gln Arg Ala Thr Met Ser Cys Arg Ala Gly Glu
50 55 60
Ser Val Asp Ile Phe Gly Val Gly Phe Leu His Trp Tyr Gln Gln Lys
65 70 75 80
Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu
85 90 95
Ser Gly Ile Pro Val Arg Phe Ser Gly Thr Gly Ser Arg Thr Asp Phe
100 105 110
Thr Leu Ile Ile Asp Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr
115 120 125
Cys Gln Gln Thr Asn Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys
130 135 140
Leu Glu Ile Lys Gly Ser Thr Ser Gly Gly Gly Ser Gly Gly Gly Ser
145 150 155 160
Gly Gly Gly Gly Ser Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu
165 170 175
Leu Val Glu Pro Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly
180 185 190
Phe Asn Ile Lys Asp Thr Tyr Met His Trp Val Lys Gln Arg Pro Glu
195 200 205
Gln Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro Ala Asn Gly Asn Ser
210 215 220
Lys Tyr Val Pro Lys Phe Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr
225 230 235 240
Ser Ser Asn Thr Ala Tyr Leu Gln Leu Thr Ser Leu Thr Ser Glu Asp
245 250 255
Thr Ala Val Tyr Tyr Cys Ala Pro Phe Gly Tyr Tyr Val Ser Asp Tyr
260 265 270
Ala Met Ala Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu
275 280 285
Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu
290 295 300
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
305 310 315 320
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
325 330 335
Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu
340 345 350
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr
355 360 365
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
370 375 380
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
385 390 395 400
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
405 410 415
Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val
420 425 430
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
435 440 445
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
450 455 460
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr
465 470 475 480
Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val
485 490 495
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
500 505 510
Ser Leu Gly Lys Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu
515 520 525
Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val
530 535 540
Arg Phe Ser Val Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe
545 550 555 560
Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly
565 570 575
Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu Arg
580 585 590
Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln
595 600 605
Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp
610 615 620
Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro
625 630 635 640
Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp
645 650 655
Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg
660 665 670
Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr
675 680 685
Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg Leu
690 695 700
<210> 10
<211> 267
<212> PRT
<213> Artificial
<220>
<223> 抗癌胚抗原(CEA)的单链抗体(scFv)的氨基酸序列
<400> 10
Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro Gly Ser Thr
1 5 10 15
Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu
20 25 30
Gly Gln Arg Ala Thr Met Ser Cys Arg Ala Gly Glu Ser Val Asp Ile
35 40 45
Phe Gly Val Gly Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Pro
50 55 60
Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Ile Pro
65 70 75 80
Val Arg Phe Ser Gly Thr Gly Ser Arg Thr Asp Phe Thr Leu Ile Ile
85 90 95
Asp Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Thr
100 105 110
Asn Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
115 120 125
Gly Ser Thr Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Gly
130 135 140
Ser Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Glu Pro
145 150 155 160
Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys
165 170 175
Asp Thr Tyr Met His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu
180 185 190
Trp Ile Gly Arg Ile Asp Pro Ala Asn Gly Asn Ser Lys Tyr Val Pro
195 200 205
Lys Phe Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr
210 215 220
Ala Tyr Leu Gln Leu Thr Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr
225 230 235 240
Tyr Cys Ala Pro Phe Gly Tyr Tyr Val Ser Asp Tyr Ala Met Ala Tyr
245 250 255
Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
260 265
<210> 11
<211> 128
<212> PRT
<213> Artificial
<220>
<223> 抗癌胚抗原(CEA)的单链抗体(scFv)的轻链可变区的氨基酸序列
<400> 11
Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro Gly Ser Thr
1 5 10 15
Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu
20 25 30
Gly Gln Arg Ala Thr Met Ser Cys Arg Ala Gly Glu Ser Val Asp Ile
35 40 45
Phe Gly Val Gly Phe Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Pro
50 55 60
Pro Lys Leu Leu Ile Tyr Arg Ala Ser Asn Leu Glu Ser Gly Ile Pro
65 70 75 80
Val Arg Phe Ser Gly Thr Gly Ser Arg Thr Asp Phe Thr Leu Ile Ile
85 90 95
Asp Pro Val Glu Ala Asp Asp Val Ala Thr Tyr Tyr Cys Gln Gln Thr
100 105 110
Asn Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
115 120 125
<210> 12
<211> 123
<212> PRT
<213> Artificial
<220>
<223> 抗癌胚抗原(CEA)的单链抗体(scFv)的重链可变区的氨基酸序列
<400> 12
Ser Ser Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Glu Pro
1 5 10 15
Gly Ala Ser Val Lys Leu Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys
20 25 30
Asp Thr Tyr Met His Trp Val Lys Gln Arg Pro Glu Gln Gly Leu Glu
35 40 45
Trp Ile Gly Arg Ile Asp Pro Ala Asn Gly Asn Ser Lys Tyr Val Pro
50 55 60
Lys Phe Gln Gly Lys Ala Thr Ile Thr Ala Asp Thr Ser Ser Asn Thr
65 70 75 80
Ala Tyr Leu Gln Leu Thr Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Ala Pro Phe Gly Tyr Tyr Val Ser Asp Tyr Ala Met Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 13
<211> 28
<212> PRT
<213> Artificial
<220>
<223> CD28跨膜区(CD28-TM)的氨基酸序列
<400> 13
Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser
1 5 10 15
Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val
20 25
<210> 14
<211> 47
<212> PRT
<213> Artificial
<220>
<223> 胞内4-1BB的氨基酸序列
<400> 14
Arg Phe Ser Val Val Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe
1 5 10 15
Lys Gln Pro Phe Met Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly
20 25 30
Cys Ser Cys Arg Phe Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu
35 40 45
<210> 15
<211> 112
<212> PRT
<213> Artificial
<220>
<223> 胞内CD3ζ的氨基酸序列
<400> 15
Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly
1 5 10 15
Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr
20 25 30
Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys
35 40 45
Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys
50 55 60
Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg
65 70 75 80
Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala
85 90 95
Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg
100 105 110
<210> 16
<211> 229
<212> PRT
<213> Artificial
<220>
<223> 免疫球蛋白IgG4铰链区片段的氨基酸序列
<400> 16
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe
1 5 10 15
Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr
20 25 30
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val
35 40 45
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val
50 55 60
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser
65 70 75 80
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu
85 90 95
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser
100 105 110
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro
115 120 125
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln
130 135 140
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala
145 150 155 160
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr
165 170 175
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu
180 185 190
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser
195 200 205
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser
210 215 220
Leu Ser Leu Gly Lys
225
Claims (18)
1.一种靶向于癌胚抗原的嵌合抗原受体,所述嵌合抗原受体包括依次连接的结合癌胚抗原的多肽、CD28跨摸区、胞内4-1BB及胞内CD3ζ。
2.根据权利要求1所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述结合癌胚抗原的多肽为抗癌胚抗原的单链抗体。
3.根据权利要求2所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述抗癌胚抗原的单链抗体包括轻链可变区和重链可变区,所述轻链可变区的氨基酸序列如SEQ IDNO.11所示,所述重链可变区的氨基酸序列如SEQ ID NO.12所示。
4.根据权利要求2所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述抗癌胚抗原的单链抗体的氨基酸序列SEQ ID NO.10所示。
5.根据权利要求1所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,还包括以下特征中的任一项或多项:(1)所述CD28跨膜区的氨基酸序列如SEQ ID NO.13所示;(2)所述胞内CD3ζ的氨基酸序列如SEQ ID NO.14所示;(3)所述胞内4-1BB的氨基酸序列如SEQ IDNO.15所示。
6.根据权利要求1所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述结合癌胚抗原的多肽与CD28跨膜区之间通过连接片段连接。
7.根据权利要求6所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述连接片段为免疫球蛋白IgD的铰链区片段。
8.根据权利要求6所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述连接片段为免疫球蛋白IgG4铰链区片段。
9.根据权利要求8所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述免疫球蛋白IgG4铰链区片段的氨基酸序列如SEQ ID NO.16所示。
10.根据权利要求1所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述结合癌胚抗原的多肽的C末端与所述CD28跨膜区的N末端连接。
11.根据权利要求1所述的靶向于癌胚抗原的嵌合抗原受体,其特征在于,所述靶向于癌胚抗原的嵌合抗原受体的氨基酸序列如SEQ ID NO.9所示。
12.一种多核苷酸,其编码如权利要求1~11任一项所述靶向于癌胚抗原的嵌合抗原受体。
13.一种表达载体,其含有如权利要求12所述多核苷酸。
14.一种宿主细胞,其被如权利要求13所述表达载体所转化。
15.一种制备如权利要求1~11任一项所述靶向于癌胚抗原的嵌合抗原受体的方法,包括步骤:构建含有靶向于癌胚抗原的嵌合抗原受体编码多核苷酸序列的表达载体,然后将所述表达载体转化至宿主细胞中诱导表达,从表达产物中分离获得所述靶向于癌胚抗原的嵌合抗原受体。
16.如权利要求1~11任一项所述靶向于癌胚抗原的嵌合抗原受体在制备嵌合抗原受体T细胞及肿瘤治疗药物中的用途。
17.一种嵌合抗原受体T细胞,其表达如权利要求1~11任一项所述靶向于癌胚抗原的嵌合抗原受体。
18.一种肿瘤治疗药物,其含有如权利要求17所述嵌合抗原受体T细胞。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710326932.9A CN107056952A (zh) | 2017-05-10 | 2017-05-10 | Cea.car‑t及其制备与应用 |
PCT/CN2017/088507 WO2018205344A1 (zh) | 2017-05-10 | 2017-06-15 | Cea.car-t及其制备与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710326932.9A CN107056952A (zh) | 2017-05-10 | 2017-05-10 | Cea.car‑t及其制备与应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN107056952A true CN107056952A (zh) | 2017-08-18 |
Family
ID=59597664
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710326932.9A Pending CN107056952A (zh) | 2017-05-10 | 2017-05-10 | Cea.car‑t及其制备与应用 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN107056952A (zh) |
WO (1) | WO2018205344A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109134666A (zh) * | 2018-09-20 | 2019-01-04 | 杭州普略生物科技有限公司 | 以cea为靶点的嵌合抗原受体 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104910279A (zh) * | 2015-06-05 | 2015-09-16 | 重庆倍思益生物科技有限公司 | 靶向癌胚抗原的嵌合抗原受体、慢病毒表达载体及其制备方法和应用 |
US9573988B2 (en) * | 2013-02-20 | 2017-02-21 | Novartis Ag | Effective targeting of primary human leukemia using anti-CD123 chimeric antigen receptor engineered T cells |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PL1976880T3 (pl) * | 2005-12-21 | 2017-01-31 | Amgen Research (Munich) Gmbh | Kompozycje farmaceutyczne odporne na rozpuszczalny cea |
CA2982603A1 (en) * | 2015-04-15 | 2016-10-20 | Prospect CharterCare RWMC, LLC d/b/a Roger Williams Medical Center | Hepatic arterial infusion of car-t cells |
CN106366178A (zh) * | 2016-08-28 | 2017-02-01 | 苏州普罗达生物科技有限公司 | 癌胚抗原免疫原多肽及其用途 |
-
2017
- 2017-05-10 CN CN201710326932.9A patent/CN107056952A/zh active Pending
- 2017-06-15 WO PCT/CN2017/088507 patent/WO2018205344A1/zh active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9573988B2 (en) * | 2013-02-20 | 2017-02-21 | Novartis Ag | Effective targeting of primary human leukemia using anti-CD123 chimeric antigen receptor engineered T cells |
CN104910279A (zh) * | 2015-06-05 | 2015-09-16 | 重庆倍思益生物科技有限公司 | 靶向癌胚抗原的嵌合抗原受体、慢病毒表达载体及其制备方法和应用 |
Non-Patent Citations (2)
Title |
---|
NEUMAIER M.等: "anti-CEA mAb T84.66, partial [Mus musculus]", 《GENBANK》 * |
NEUMAIER M.等: "anti-CEA mAb T84.66, partial [Mus musculus]", 《GENKANK》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109134666A (zh) * | 2018-09-20 | 2019-01-04 | 杭州普略生物科技有限公司 | 以cea为靶点的嵌合抗原受体 |
CN109134666B (zh) * | 2018-09-20 | 2020-08-21 | 杭州普略生物科技有限公司 | 以cea为靶点的嵌合抗原受体 |
Also Published As
Publication number | Publication date |
---|---|
WO2018205344A1 (zh) | 2018-11-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111629734A (zh) | 用于共刺激的新型平台、新型car设计以及过继性细胞疗法的其他增强 | |
US10093746B2 (en) | Glypican-3 antibody and uses thereof | |
JP2022002516A (ja) | 癌を治療するためのキメラ抗原受容体改変t細胞の使用 | |
JP2020058380A (ja) | キメラ抗原受容体及びその製造方法 | |
CN110291402A (zh) | 鉴定肽表位的方法、结合此类表位的分子和相关用途 | |
CN109937364A (zh) | Mhc-e限制性表位、结合分子以及相关方法和用途 | |
CN108948211B (zh) | 一种基于靶向gd2的嵌合抗原受体及其应用 | |
CN107106670A (zh) | 用于修饰的t细胞的方法和组合物 | |
CN108137670A (zh) | Ny-eso-1特异性tcr及其使用方法 | |
CN113260368A (zh) | 抗gpc3嵌合抗原受体(car)与反式共刺激分子的组合及其治疗用途 | |
CN112888786A (zh) | 与调节细胞内乳酸浓度的反式代谢分子组合的嵌合受体多肽及其治疗用途 | |
JP2015524255A (ja) | 二重特異性抗体を共導入することによってcart細胞の活性を強化する方法 | |
CN110234756A (zh) | 转导和扩增免疫细胞的方法及其用途 | |
CN112638402A (zh) | 与增强葡萄糖输入的反式代谢分子组合的嵌合受体及其治疗用途 | |
CN107365798A (zh) | 一种携带iCasp9自杀基因的CD19‑CAR‑T细胞及其应用 | |
AU2018242408B2 (en) | Chimeric antigen receptor | |
CN115052902A (zh) | 淋巴细胞-抗原提呈细胞共刺激因子及其应用 | |
CN107868791A (zh) | 一种加强型Slit2 CAR‑T和CAR‑NK细胞制备方法和应用 | |
US20170354681A1 (en) | T cell-based immunotherapeutics | |
KR20230006821A (ko) | 변형 b 세포 및 이의 사용 방법 | |
CN114585371A (zh) | 嵌合抑制性受体 | |
CN107058234B (zh) | Car.il-33-t及其制备与应用 | |
CN107188968A (zh) | 一种靶向pdpn基因的人源嵌合抗原受体及其用途 | |
CN110423767A (zh) | 表达可溶性pd-1的嵌合抗原受体car基因及应用 | |
CN110078830A (zh) | 一种在共刺激结构域上携带重复活化基序的嵌合抗原受体t细胞 |
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 | ||
CB03 | Change of inventor or designer information |
Inventor after: Jiang Jingting Inventor after: Lu Binfeng Inventor after: Chen Yuang Inventor after: Chen Lujun Inventor before: Jiang Jingting Inventor before: Lu Binfeng Inventor before: Chen Yuang Inventor before: Chen Lujun |
|
CB03 | Change of inventor or designer information | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170818 |
|
RJ01 | Rejection of invention patent application after publication |