CN1157570A - 化学药物向特定细胞的细胞内载运 - Google Patents
化学药物向特定细胞的细胞内载运 Download PDFInfo
- Publication number
- CN1157570A CN1157570A CN95195037A CN95195037A CN1157570A CN 1157570 A CN1157570 A CN 1157570A CN 95195037 A CN95195037 A CN 95195037A CN 95195037 A CN95195037 A CN 95195037A CN 1157570 A CN1157570 A CN 1157570A
- Authority
- CN
- China
- Prior art keywords
- chemicals
- cell
- seq
- receptor
- compositions
- 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
- 230000003834 intracellular effect Effects 0.000 title claims abstract description 8
- 239000013043 chemical agent Substances 0.000 title abstract 6
- 239000000203 mixture Substances 0.000 claims abstract description 99
- 108010023729 Complement 3d Receptors Proteins 0.000 claims abstract description 54
- 102000011412 Complement 3d Receptors Human genes 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 47
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 23
- 230000012202 endocytosis Effects 0.000 claims abstract description 20
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 20
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 20
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 20
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 19
- 239000002619 cytotoxin Substances 0.000 claims abstract description 18
- 231100000599 cytotoxic agent Toxicity 0.000 claims abstract description 17
- 102000036639 antigens Human genes 0.000 claims abstract description 16
- 108091007433 antigens Proteins 0.000 claims abstract description 16
- 239000000427 antigen Substances 0.000 claims abstract description 15
- 239000002502 liposome Substances 0.000 claims abstract description 8
- 230000001939 inductive effect Effects 0.000 claims abstract description 7
- 239000003446 ligand Substances 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 160
- 239000000126 substance Substances 0.000 claims description 130
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 67
- 108010039491 Ricin Proteins 0.000 claims description 44
- 230000004927 fusion Effects 0.000 claims description 36
- 230000000694 effects Effects 0.000 claims description 18
- 101710112752 Cytotoxin Proteins 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- -1 label Substances 0.000 claims description 13
- 230000033228 biological regulation Effects 0.000 claims description 10
- 210000004698 lymphocyte Anatomy 0.000 claims description 9
- 210000001185 bone marrow Anatomy 0.000 claims description 7
- 238000002372 labelling Methods 0.000 claims description 7
- 229920001503 Glucan Polymers 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 6
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 6
- 239000013612 plasmid Substances 0.000 claims description 6
- 230000010837 receptor-mediated endocytosis Effects 0.000 claims description 6
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 5
- 102100032768 Complement receptor type 2 Human genes 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 4
- 238000013467 fragmentation Methods 0.000 claims 8
- 238000006062 fragmentation reaction Methods 0.000 claims 8
- 125000003275 alpha amino acid group Chemical group 0.000 claims 7
- 229940079593 drug Drugs 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 2
- 230000008878 coupling Effects 0.000 abstract 1
- 238000010168 coupling process Methods 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 125000006850 spacer group Chemical group 0.000 abstract 1
- 230000001131 transforming effect Effects 0.000 abstract 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 27
- 150000001413 amino acids Chemical group 0.000 description 22
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 238000005516 engineering process Methods 0.000 description 13
- 230000002121 endocytic effect Effects 0.000 description 12
- 108091034117 Oligonucleotide Proteins 0.000 description 11
- 230000029087 digestion Effects 0.000 description 11
- 239000004365 Protease Substances 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 9
- 108091005804 Peptidases Proteins 0.000 description 8
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 108020004511 Recombinant DNA Proteins 0.000 description 6
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 6
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- 108010052926 complement C3d,g Proteins 0.000 description 6
- 102000037865 fusion proteins Human genes 0.000 description 6
- 108020001507 fusion proteins Proteins 0.000 description 6
- 239000004325 lysozyme Substances 0.000 description 6
- 229960000274 lysozyme Drugs 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000001488 sodium phosphate Substances 0.000 description 6
- 229910000162 sodium phosphate Inorganic materials 0.000 description 6
- 231100000167 toxic agent Toxicity 0.000 description 6
- 239000003440 toxic substance Substances 0.000 description 6
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 102000016943 Muramidase Human genes 0.000 description 4
- 108010014251 Muramidase Proteins 0.000 description 4
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 4
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 210000002919 epithelial cell Anatomy 0.000 description 4
- 108010013768 glutamyl-aspartyl-proline Proteins 0.000 description 4
- 235000010335 lysozyme Nutrition 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 238000005215 recombination Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000000527 sonication Methods 0.000 description 4
- 238000007910 systemic administration Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- CKOFNWCLWRYUHK-XHNCKOQMSA-N Glu-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O CKOFNWCLWRYUHK-XHNCKOQMSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 3
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 238000009413 insulation Methods 0.000 description 3
- 210000002751 lymph Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- DIYPCWKHSODVAP-UHFFFAOYSA-N 1-[3-(2,5-dioxopyrrol-1-yl)benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 DIYPCWKHSODVAP-UHFFFAOYSA-N 0.000 description 2
- RTFWCVDISAMGEQ-SRVKXCTJSA-N Asn-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](CC(=O)N)N RTFWCVDISAMGEQ-SRVKXCTJSA-N 0.000 description 2
- MYRLSKYSMXNLLA-LAEOZQHASA-N Asn-Val-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MYRLSKYSMXNLLA-LAEOZQHASA-N 0.000 description 2
- HICVMZCGVFKTPM-BQBZGAKWSA-N Asp-Pro-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O HICVMZCGVFKTPM-BQBZGAKWSA-N 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 108010074124 Escherichia coli Proteins Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-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
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- 235000004443 Ricinus communis Nutrition 0.000 description 2
- 240000000528 Ricinus communis Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 108010081551 glycylphenylalanine Proteins 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 108010028295 histidylhistidine Proteins 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 210000003519 mature b lymphocyte Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003104 tissue culture media Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 108020005096 28S Ribosomal RNA Proteins 0.000 description 1
- RXGJTUSBYWCRBK-UHFFFAOYSA-M 5-methylphenazinium methyl sulfate Chemical compound COS([O-])(=O)=O.C1=CC=C2[N+](C)=C(C=CC=C3)C3=NC2=C1 RXGJTUSBYWCRBK-UHFFFAOYSA-M 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101100256850 Drosophila melanogaster EndoA gene Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- BXICSAQLIHFDDL-YUMQZZPRSA-N Gly-Lys-Asn Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O BXICSAQLIHFDDL-YUMQZZPRSA-N 0.000 description 1
- FEUPVVCGQLNXNP-IRXDYDNUSA-N Gly-Phe-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 FEUPVVCGQLNXNP-IRXDYDNUSA-N 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- STOOMQFEJUVAKR-KKUMJFAQSA-N His-His-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)C1=CNC=N1 STOOMQFEJUVAKR-KKUMJFAQSA-N 0.000 description 1
- CMNMPCTVCWWYHY-MXAVVETBSA-N Ile-His-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC(C)C)C(=O)O)N CMNMPCTVCWWYHY-MXAVVETBSA-N 0.000 description 1
- MFGOTAHWOBKNNU-XMHGGMMESA-N Isodigeranyl Chemical group CC(C)=CCC\C(C)=C\CC(C)(C=C)CCC=C(C)C MFGOTAHWOBKNNU-XMHGGMMESA-N 0.000 description 1
- MFGOTAHWOBKNNU-FQEVSTJZSA-N Isodigeranyl Natural products CC(=CCCC(=CC[C@](C)(CCC=C(C)C)C=C)C)C MFGOTAHWOBKNNU-FQEVSTJZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- WUHBLPVELFTPQK-KKUMJFAQSA-N Leu-Tyr-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O WUHBLPVELFTPQK-KKUMJFAQSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- JIYJYFIXQTYDNF-YDHLFZDLSA-N Phe-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC1=CC=CC=C1)N JIYJYFIXQTYDNF-YDHLFZDLSA-N 0.000 description 1
- OWSLLRKCHLTUND-BZSNNMDCSA-N Phe-Phe-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(=O)N)C(=O)O)N OWSLLRKCHLTUND-BZSNNMDCSA-N 0.000 description 1
- 239000012564 Q sepharose fast flow resin Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- AQAMPXBRJJWPNI-JHEQGTHGSA-N Thr-Gly-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O AQAMPXBRJJWPNI-JHEQGTHGSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 102000025171 antigen binding proteins Human genes 0.000 description 1
- 108091000831 antigen binding proteins Proteins 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000000678 band cell Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000005179 haloacetyl group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 1
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 108010003052 omptin outer membrane protease Proteins 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000012771 pancakes Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 101150079601 recA gene Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/472—Complement proteins, e.g. anaphylatoxin, C3a, C5a
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
- A61K39/385—Haptens or antigens, bound to carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/6425—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16211—Lymphocryptovirus, e.g. human herpesvirus 4, Epstein-Barr Virus
- C12N2710/16222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cell Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Virology (AREA)
- Mycology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30577094A | 1994-09-13 | 1994-09-13 | |
US08/305,770 | 1994-09-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1157570A true CN1157570A (zh) | 1997-08-20 |
Family
ID=23182273
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN95195037A Pending CN1157570A (zh) | 1994-09-13 | 1995-09-12 | 化学药物向特定细胞的细胞内载运 |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP0781139A1 (xx) |
JP (1) | JPH10505835A (xx) |
KR (1) | KR970705404A (xx) |
CN (1) | CN1157570A (xx) |
AU (1) | AU697469B2 (xx) |
BR (1) | BR9508951A (xx) |
CA (1) | CA2198361A1 (xx) |
CZ (1) | CZ74797A3 (xx) |
HU (1) | HUT77263A (xx) |
MX (1) | MX9701860A (xx) |
PL (1) | PL319100A1 (xx) |
WO (1) | WO1996008263A1 (xx) |
ZA (1) | ZA957688B (xx) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1616665B (zh) * | 1997-11-19 | 2010-10-06 | 乔治敦大学 | 定向脂质体基因送递 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6251866B1 (en) | 1997-08-05 | 2001-06-26 | Watson Laboratories, Inc. | Conjugates targeted to the interleukin-2 receptor |
WO1999007324A2 (en) * | 1997-08-05 | 1999-02-18 | Watson Pharmaceuticals, Inc. | Conjugates targeted to the interleukin-2 receptor |
DE19926154A1 (de) * | 1999-06-09 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Verfahren zur Herstellung einer injizierbaren Arzneimittelzubereitung |
GB9922554D0 (en) * | 1999-09-23 | 1999-11-24 | Microbiological Res Authority | Inhibition of secretion from non-neuronal cells |
US10806803B2 (en) | 2014-07-17 | 2020-10-20 | Ohio State Innovation Foundation | Compositions for targeting macrophages and other CD206 high expressing cells and methods of treating and diagnosis |
US11007272B1 (en) | 2016-10-07 | 2021-05-18 | Navidea Biopharmaceuticals, Inc. | Compounds and methods for diagnosis and treatment of viral infections |
WO2023225273A1 (en) | 2022-05-20 | 2023-11-23 | Navidea Biopharmaceuticals, Inc. | Cd206 targeted drug delivery vehicles carrying novel bisphosphonate drug payloads via a degradable linker |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5135736A (en) * | 1988-08-15 | 1992-08-04 | Neorx Corporation | Covalently-linked complexes and methods for enhanced cytotoxicity and imaging |
US5331090A (en) * | 1989-09-08 | 1994-07-19 | California Institute Of Biological Research | CR2 ligand compositions and methods for modulating immune cell functions |
US5165923A (en) * | 1989-11-20 | 1992-11-24 | Imperial Cancer Research Technology | Methods and compositions for the treatment of hodgkin's disease |
-
1995
- 1995-09-12 BR BR9508951A patent/BR9508951A/pt not_active Application Discontinuation
- 1995-09-12 CN CN95195037A patent/CN1157570A/zh active Pending
- 1995-09-12 WO PCT/US1995/011515 patent/WO1996008263A1/en not_active Application Discontinuation
- 1995-09-12 HU HU9701746A patent/HUT77263A/hu unknown
- 1995-09-12 AU AU35507/95A patent/AU697469B2/en not_active Ceased
- 1995-09-12 EP EP95932472A patent/EP0781139A1/en not_active Withdrawn
- 1995-09-12 MX MX9701860A patent/MX9701860A/es unknown
- 1995-09-12 PL PL95319100A patent/PL319100A1/xx unknown
- 1995-09-12 KR KR1019970701469A patent/KR970705404A/ko not_active Application Discontinuation
- 1995-09-12 JP JP8510273A patent/JPH10505835A/ja active Pending
- 1995-09-12 CZ CZ97747A patent/CZ74797A3/cs unknown
- 1995-09-12 CA CA002198361A patent/CA2198361A1/en not_active Abandoned
- 1995-09-13 ZA ZA957688A patent/ZA957688B/xx unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1616665B (zh) * | 1997-11-19 | 2010-10-06 | 乔治敦大学 | 定向脂质体基因送递 |
Also Published As
Publication number | Publication date |
---|---|
PL319100A1 (en) | 1997-07-21 |
CZ74797A3 (en) | 1997-08-13 |
MX9701860A (es) | 1997-06-28 |
KR970705404A (ko) | 1997-10-09 |
BR9508951A (pt) | 1999-04-06 |
AU697469B2 (en) | 1998-10-08 |
AU3550795A (en) | 1996-03-29 |
HUT77263A (hu) | 1998-03-02 |
JPH10505835A (ja) | 1998-06-09 |
WO1996008263A1 (en) | 1996-03-21 |
ZA957688B (en) | 1996-05-13 |
CA2198361A1 (en) | 1996-03-21 |
EP0781139A1 (en) | 1997-07-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1184235C (zh) | 嵌合多肽、其产生方法及应用 | |
JP2996415B2 (ja) | 巨核球の成長と分化を刺激するモノpeg化mgdfポリペプチド | |
EP3352782B1 (en) | Improved methods and compounds for eliminating immune responses to therapeutic agents | |
CN1713920A (zh) | 被修饰的转铁蛋白融合蛋白 | |
CN1680451A (zh) | 包含hpv抗原和应激蛋白或者其表达载体的组合物激发的抗hpv抗原免疫应答 | |
CN1067679A (zh) | 重组dna衍生的霍乱毒素亚基类似物 | |
CN104245722A (zh) | 白细胞介素-10多肽结合物和其用途 | |
WO1996019584A9 (en) | Chimeric antibodies comprising antigen binding sites and b and t cell epitopes | |
CN1134111A (zh) | 使用胰岛素样生长因子结合蛋白质的方法 | |
JPS63501799A (ja) | Cysコドン修飾DNA | |
CN1791679A (zh) | 基于CD8α链的具有降低的免疫原性的基因治疗载体 | |
KR20140069222A (ko) | 교차 제시 수지상 세포를 표적으로 하는 백시바디 | |
CN104245720A (zh) | 白细胞介素-3多肽结合物和其用途 | |
EP2056859B1 (en) | Promiscuous pap cd4 t cell epitopes | |
CN1157570A (zh) | 化学药物向特定细胞的细胞内载运 | |
CN1178950C (zh) | 司登尼亚蛋白小体-司登尼亚钙蛋白 | |
CN1151760A (zh) | 血清对氧磷酶 | |
JP2510846B2 (ja) | PE40Abを含有するタンパク質抗ガン剤 | |
US5194592A (en) | Monoclonal antibodies to novel polypeptide derivatives of human granulocyte colony stimulating factor | |
EP0728015B1 (en) | Method of producing a set of combinatorial polypeptide antigens | |
CN1299833A (zh) | 抗人血管内皮生长因子单链抗体及其制备方法 | |
MXPA97001860A (en) | Intracellular supply of chemical agents, to a specific unit of cel | |
CN1235910C (zh) | 与短肽激素嵌合的靶特异性细胞毒性剂 | |
CN1966529A (zh) | 含有促性腺激素释放素和绿脓毒素功能片段的重组毒性剂 | |
JPH02502287A (ja) | 改良されたリシン分子およびリシン毒素コンジュゲート |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C01 | Deemed withdrawal of patent application (patent law 1993) | ||
WD01 | Invention patent application deemed withdrawn after publication |