JP5166025B2 - エピトープアナログ - Google Patents
エピトープアナログ Download PDFInfo
- Publication number
- JP5166025B2 JP5166025B2 JP2007516810A JP2007516810A JP5166025B2 JP 5166025 B2 JP5166025 B2 JP 5166025B2 JP 2007516810 A JP2007516810 A JP 2007516810A JP 2007516810 A JP2007516810 A JP 2007516810A JP 5166025 B2 JP5166025 B2 JP 5166025B2
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- analogs
- binding
- analog
- mhc
- 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.)
- Expired - Fee Related
Links
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 523
- 230000027455 binding Effects 0.000 claims description 216
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 126
- 239000000203 mixture Substances 0.000 claims description 39
- 150000007523 nucleic acids Chemical class 0.000 claims description 32
- 230000002163 immunogen Effects 0.000 claims description 31
- 108020004707 nucleic acids Proteins 0.000 claims description 31
- 102000039446 nucleic acids Human genes 0.000 claims description 31
- 230000004044 response Effects 0.000 claims description 30
- 102000025850 HLA-A2 Antigen Human genes 0.000 claims description 25
- 108010074032 HLA-A2 Antigen Proteins 0.000 claims description 25
- 229920001184 polypeptide Polymers 0.000 claims description 23
- 230000001939 inductive effect Effects 0.000 claims description 14
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 claims description 8
- 230000005867 T cell response Effects 0.000 claims description 6
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 claims description 5
- 230000000091 immunopotentiator Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims 3
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 description 212
- 229940024606 amino acid Drugs 0.000 description 204
- 150000001413 amino acids Chemical class 0.000 description 193
- 238000006467 substitution reaction Methods 0.000 description 190
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 129
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 120
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 117
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 115
- 230000001976 improved effect Effects 0.000 description 115
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 109
- 230000000694 effects Effects 0.000 description 92
- 108091008874 T cell receptors Proteins 0.000 description 82
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 81
- 210000001744 T-lymphocyte Anatomy 0.000 description 80
- 238000000034 method Methods 0.000 description 78
- 210000004027 cell Anatomy 0.000 description 77
- 239000000427 antigen Substances 0.000 description 73
- 230000009260 cross reactivity Effects 0.000 description 71
- 108091007433 antigens Proteins 0.000 description 70
- 102000036639 antigens Human genes 0.000 description 70
- 230000003993 interaction Effects 0.000 description 66
- 206010028980 Neoplasm Diseases 0.000 description 63
- 230000004048 modification Effects 0.000 description 54
- 238000012986 modification Methods 0.000 description 54
- 102000036673 PRAME Human genes 0.000 description 53
- 108060006580 PRAME Proteins 0.000 description 53
- 102100037850 Interferon gamma Human genes 0.000 description 45
- 108010074328 Interferon-gamma Proteins 0.000 description 45
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 44
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 44
- 238000003556 assay Methods 0.000 description 42
- 238000001727 in vivo Methods 0.000 description 41
- 239000013612 plasmid Substances 0.000 description 41
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 39
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 39
- QWCKQJZIFLGMSD-UHFFFAOYSA-N alpha-aminobutyric acid Chemical compound CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 38
- 230000028993 immune response Effects 0.000 description 37
- 230000003053 immunization Effects 0.000 description 35
- 238000002649 immunization Methods 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 34
- 210000004988 splenocyte Anatomy 0.000 description 34
- 230000001965 increasing effect Effects 0.000 description 33
- 238000004519 manufacturing process Methods 0.000 description 33
- 231100000135 cytotoxicity Toxicity 0.000 description 32
- 230000003013 cytotoxicity Effects 0.000 description 32
- 230000005847 immunogenicity Effects 0.000 description 32
- 108010075704 HLA-A Antigens Proteins 0.000 description 30
- 102000011786 HLA-A Antigens Human genes 0.000 description 30
- 210000004899 c-terminal region Anatomy 0.000 description 29
- 210000001165 lymph node Anatomy 0.000 description 29
- 210000004881 tumor cell Anatomy 0.000 description 28
- XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 description 27
- 102000003425 Tyrosinase Human genes 0.000 description 26
- 108060008724 Tyrosinase Proteins 0.000 description 26
- 108091054437 MHC class I family Proteins 0.000 description 25
- 230000001900 immune effect Effects 0.000 description 25
- 230000036039 immunity Effects 0.000 description 25
- -1 Tyr Chemical class 0.000 description 23
- 201000011510 cancer Diseases 0.000 description 23
- 238000000338 in vitro Methods 0.000 description 23
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 22
- 102000043129 MHC class I family Human genes 0.000 description 22
- 125000003275 alpha amino acid group Chemical group 0.000 description 22
- 238000011830 transgenic mouse model Methods 0.000 description 21
- 241000699660 Mus musculus Species 0.000 description 19
- 230000002209 hydrophobic effect Effects 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 19
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 18
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 17
- 230000016396 cytokine production Effects 0.000 description 17
- GTVVZTAFGPQSPC-UHFFFAOYSA-N 4-nitrophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-UHFFFAOYSA-N 0.000 description 15
- 238000013461 design Methods 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 14
- 230000000875 corresponding effect Effects 0.000 description 14
- 230000006872 improvement Effects 0.000 description 14
- 239000013642 negative control Substances 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- 230000000717 retained effect Effects 0.000 description 14
- 108010010995 MART-1 Antigen Proteins 0.000 description 13
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 101150080480 A27L gene Proteins 0.000 description 12
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 12
- 101100268532 Vaccinia virus (strain Western Reserve) VACWR150 gene Proteins 0.000 description 12
- 102200151424 rs5198 Human genes 0.000 description 12
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 11
- 125000000539 amino acid group Chemical group 0.000 description 11
- 230000009089 cytolysis Effects 0.000 description 11
- 238000011156 evaluation Methods 0.000 description 11
- 125000001165 hydrophobic group Chemical class 0.000 description 11
- 229960005486 vaccine Drugs 0.000 description 11
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 10
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 10
- 201000001441 melanoma Diseases 0.000 description 10
- 210000000952 spleen Anatomy 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 238000000684 flow cytometry Methods 0.000 description 9
- 238000010186 staining Methods 0.000 description 9
- 108700028369 Alleles Proteins 0.000 description 8
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 8
- 102100039510 Cancer/testis antigen 2 Human genes 0.000 description 8
- 101000889345 Homo sapiens Cancer/testis antigen 2 Proteins 0.000 description 8
- 235000004279 alanine Nutrition 0.000 description 8
- 150000001408 amides Chemical group 0.000 description 8
- 238000010494 dissociation reaction Methods 0.000 description 8
- 230000005593 dissociations Effects 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 7
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 7
- 108010066345 MHC binding peptide Proteins 0.000 description 7
- 208000024313 Testicular Neoplasms Diseases 0.000 description 7
- 206010057644 Testis cancer Diseases 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000011081 inoculation Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 201000003120 testicular cancer Diseases 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 6
- 210000000612 antigen-presenting cell Anatomy 0.000 description 6
- 238000004422 calculation algorithm Methods 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical group C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
- 101100462972 Mus musculus Pcdh8 gene Proteins 0.000 description 5
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 5
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 5
- 230000003321 amplification Effects 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 230000006037 cell lysis Effects 0.000 description 5
- 231100000433 cytotoxic Toxicity 0.000 description 5
- 230000001472 cytotoxic effect Effects 0.000 description 5
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 5
- 230000007717 exclusion Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 230000037452 priming Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 239000004474 valine Substances 0.000 description 5
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 4
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000880770 Homo sapiens Protein SSX2 Proteins 0.000 description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 4
- 102100037686 Protein SSX2 Human genes 0.000 description 4
- 230000001772 anti-angiogenic effect Effects 0.000 description 4
- 150000001491 aromatic compounds Chemical class 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 230000002596 correlated effect Effects 0.000 description 4
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 238000009795 derivation Methods 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 238000009169 immunotherapy Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- LZOIGVDSAMDBIO-LXWJMTKESA-N (2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-4-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoic acid Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](N)CCSC)C1=CC=CC=C1 LZOIGVDSAMDBIO-LXWJMTKESA-N 0.000 description 3
- KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- QWCKQJZIFLGMSD-VKHMYHEASA-N L-alpha-aminobutyric acid Chemical compound CC[C@H](N)C(O)=O QWCKQJZIFLGMSD-VKHMYHEASA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102100037020 Melanoma antigen preferentially expressed in tumors Human genes 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- GEYBMYRBIABFTA-VIFPVBQESA-N O-methyl-L-tyrosine Chemical compound COC1=CC=C(C[C@H](N)C(O)=O)C=C1 GEYBMYRBIABFTA-VIFPVBQESA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- DZHDVYLBNKMLMB-ZFWWWQNUSA-N Trp-Lys Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCCCN)C(O)=O)=CNC2=C1 DZHDVYLBNKMLMB-ZFWWWQNUSA-N 0.000 description 3
- 230000006229 amino acid addition Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000001461 cytolytic effect Effects 0.000 description 3
- 238000001212 derivatisation Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- UKAUYVFTDYCKQA-UHFFFAOYSA-N homoserine Chemical compound OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 210000002751 lymph Anatomy 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- 101001095088 Homo sapiens Melanoma antigen preferentially expressed in tumors Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 102000007557 Melanoma-Specific Antigens Human genes 0.000 description 2
- 108010071463 Melanoma-Specific Antigens Proteins 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 229920000361 Poly(styrene)-block-poly(ethylene glycol) Polymers 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 108010077895 Sarcosine Proteins 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 239000004473 Threonine Chemical group 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical group CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002784 cytotoxicity assay Methods 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000001712 encephalitogenic effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000005965 immune activity Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012925 reference material Substances 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000002483 superagonistic effect Effects 0.000 description 2
- 206010042863 synovial sarcoma Diseases 0.000 description 2
- 238000011191 terminal modification Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
- GTVVZTAFGPQSPC-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(4-nitrophenyl)propanoate Chemical class OC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-QMMMGPOBSA-N 0.000 description 1
- POVNCJSPYFCWJR-USZUGGBUSA-N (4s)-4-[[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-5-[(2s)-2-[[2-[(2s)-2-[[(2s)-1-[[(2s,3r)-1-[[(1s)-1-carboxy-2-methylpropyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1- Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O)C1=CC=C(O)C=C1 POVNCJSPYFCWJR-USZUGGBUSA-N 0.000 description 1
- KPYXMALABCDPGN-HYOZMBHHSA-N (4s)-5-[[(2s)-6-amino-1-[[(2s,3s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[2-[[2-[[(1s)-3-amino-1-carboxy-3-oxopropyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]a Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN)CC1=CC=C(O)C=C1 KPYXMALABCDPGN-HYOZMBHHSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical group C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- XWHHYOYVRVGJJY-UHFFFAOYSA-N 4-fluorophenylalanine Chemical compound OC(=O)C(N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-UHFFFAOYSA-N 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102100035526 B melanoma antigen 1 Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 102100025933 Cancer-associated gene 1 protein Human genes 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000011510 Elispot assay Methods 0.000 description 1
- MBYXEBXZARTUSS-QLWBXOBMSA-N Emetamine Natural products O(C)c1c(OC)cc2c(c(C[C@@H]3[C@H](CC)CN4[C@H](c5c(cc(OC)c(OC)c5)CC4)C3)ncc2)c1 MBYXEBXZARTUSS-QLWBXOBMSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102220551767 Guanylate-binding protein 1_I46L_mutation Human genes 0.000 description 1
- 102220473084 HLA class II histocompatibility antigen, DP alpha 1 chain_A42M_mutation Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 101000874316 Homo sapiens B melanoma antigen 1 Proteins 0.000 description 1
- 101000933825 Homo sapiens Cancer-associated gene 1 protein Proteins 0.000 description 1
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 1
- 101100137533 Homo sapiens PRAME gene Proteins 0.000 description 1
- 101001094545 Homo sapiens Retrotransposon-like protein 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- 125000000205 L-threonino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])[C@](C([H])([H])[H])([H])O[H] 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- 102000016200 MART-1 Antigen Human genes 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
- NSTPXGARCQOSAU-VIFPVBQESA-N N-formyl-L-phenylalanine Chemical class O=CN[C@H](C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-VIFPVBQESA-N 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 101800001357 Potential peptide Proteins 0.000 description 1
- 102400000745 Potential peptide Human genes 0.000 description 1
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- DSLZVSRJTYRBFB-GNSDDBTRSA-N allaric acid Chemical group OC(=O)[C@@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-GNSDDBTRSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000002547 anomalous effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 108010083141 dipeptidyl carboxypeptidase Proteins 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
- 229960002694 emetine Drugs 0.000 description 1
- AUVVAXYIELKVAI-UWBTVBNJSA-N emetine Natural products N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@H]1CC AUVVAXYIELKVAI-UWBTVBNJSA-N 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000012737 microarray-based gene expression Methods 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000012243 multiplex automated genomic engineering Methods 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 230000016412 positive regulation of cytokine production Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 102200100439 rs2304681 Human genes 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000013515 script Methods 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 108010042703 synovial sarcoma X breakpoint proteins Proteins 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000009258 tissue cross reactivity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
-
- 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
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58100104P | 2004-06-17 | 2004-06-17 | |
| US58096204P | 2004-06-17 | 2004-06-17 | |
| US60/580,962 | 2004-06-17 | ||
| US60/581,001 | 2004-06-17 | ||
| PCT/US2005/021609 WO2006009920A2 (en) | 2004-06-17 | 2005-06-17 | Epitope analogs |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008155749A Division JP2008283979A (ja) | 2004-06-17 | 2008-06-13 | エピトープアナログ |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008510453A JP2008510453A (ja) | 2008-04-10 |
| JP2008510453A5 JP2008510453A5 (enExample) | 2008-08-07 |
| JP5166025B2 true JP5166025B2 (ja) | 2013-03-21 |
Family
ID=35198081
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007516810A Expired - Fee Related JP5166025B2 (ja) | 2004-06-17 | 2005-06-17 | エピトープアナログ |
| JP2008155749A Ceased JP2008283979A (ja) | 2004-06-17 | 2008-06-13 | エピトープアナログ |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008155749A Ceased JP2008283979A (ja) | 2004-06-17 | 2008-06-13 | エピトープアナログ |
Country Status (10)
| Country | Link |
|---|---|
| US (5) | US8354380B2 (enExample) |
| EP (2) | EP2332971B1 (enExample) |
| JP (2) | JP5166025B2 (enExample) |
| KR (2) | KR20070056042A (enExample) |
| AU (1) | AU2005265182B2 (enExample) |
| CA (1) | CA2571168A1 (enExample) |
| IL (2) | IL180101A (enExample) |
| MX (1) | MXPA06014768A (enExample) |
| SG (1) | SG153827A1 (enExample) |
| WO (1) | WO2006009920A2 (enExample) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6977074B2 (en) | 1997-07-10 | 2005-12-20 | Mannkind Corporation | Method of inducing a CTL response |
| US7178491B2 (en) * | 2003-06-05 | 2007-02-20 | Caterpillar Inc | Control system and method for engine valve actuator |
| US20060159689A1 (en) * | 2004-06-17 | 2006-07-20 | Chih-Sheng Chiang | Combinations of tumor-associated antigens in diagnostics for various types of cancers |
| JP2008503494A (ja) * | 2004-06-17 | 2008-02-07 | マンカインド コーポレイション | 診断方法を治療方法と統合することによる免疫療法の効力改善 |
| EP2332971B1 (en) | 2004-06-17 | 2016-02-17 | MannKind Corporation | Epitope analogs |
| US20060008468A1 (en) * | 2004-06-17 | 2006-01-12 | Chih-Sheng Chiang | Combinations of tumor-associated antigens in diagnostics for various types of cancers |
| KR101294290B1 (ko) * | 2004-12-29 | 2013-08-07 | 맨카인드 코포레이션 | 예방 또는 치료를 위해 제i류 주조직 적합성복합체〔mhc〕-제한 에피토프에 대한 면역 반응을 유발,향상 및 지속하는 방법 |
| AU2005321898B2 (en) * | 2004-12-29 | 2012-07-19 | Mannkind Corporation | Use of compositions comprising various tumor-associated antigens as anti-cancer vaccines |
| EP1838342A2 (en) * | 2004-12-29 | 2007-10-03 | Mannkind Corporation | Methods to bypass cd+4 cells in the induction of an immune response |
| EP2351576A1 (en) * | 2004-12-29 | 2011-08-03 | Mannkind Corporation | Methods to trigger, maintain and manipulate immune responses by targeted administration of biological response modifiers into lymphoid organs |
| US7511119B2 (en) | 2005-06-17 | 2009-03-31 | Mannkind Corporation | PRAME peptide analogues |
| KR20080033271A (ko) | 2005-06-17 | 2008-04-16 | 맨카인드 코포레이션 | 암종을 위한 다가 동반이행 및 증폭형 면역치료제 |
| CA2612516C (en) | 2005-06-17 | 2015-03-24 | Mannkind Corporation | Methods and compositions to elicit multivalent immune responses against dominant and subdominant epitopes, expressed on cancer cells and tumor stroma |
| US8706421B2 (en) * | 2006-02-16 | 2014-04-22 | Microsoft Corporation | Shift-invariant predictions |
| US20070192033A1 (en) * | 2006-02-16 | 2007-08-16 | Microsoft Corporation | Molecular interaction predictors |
| US8396671B2 (en) * | 2006-02-16 | 2013-03-12 | Microsoft Corporation | Cluster modeling, and learning cluster specific parameters of an adaptive double threading model |
| CN1850855B (zh) * | 2006-05-26 | 2012-08-29 | 厦门大学 | 用于免疫或制备单克隆抗体的方法和组合物 |
| US20080014211A1 (en) * | 2006-07-14 | 2008-01-17 | Mannkind Corporation | Methods to elicit, enhance and sustain immune responses against MHC class I-restricted epitopes, for prophylactic and therapeutic purposes |
| PT2476435T (pt) | 2006-08-11 | 2018-03-05 | Life Sciences Res Partners Vzw | Péptidos imunogénicos e a sua utilização em distúrbios imunitários |
| US8121797B2 (en) * | 2007-01-12 | 2012-02-21 | Microsoft Corporation | T-cell epitope prediction |
| EP2129389B1 (en) * | 2007-02-15 | 2014-10-08 | MannKind Corporation | A method for enhancing t cell response |
| CN106220721B (zh) | 2007-03-26 | 2020-04-07 | 莱顿大学医学中心附属莱顿教学医院 | Prame衍生的肽以及包括该肽的免疫原组合物 |
| JP2010528591A (ja) * | 2007-05-23 | 2010-08-26 | マンカインド コーポレイション | マルチシストロン性ベクター及びそれらの設計方法 |
| US8999346B2 (en) | 2008-02-14 | 2015-04-07 | Life Sciences Research Partners Vzw | Immunogenic control of tumours and tumour cells |
| WO2011050344A2 (en) | 2009-10-23 | 2011-04-28 | Mannkind Corporation | Cancer immunotherapy and method of treatment |
| EP3018146A1 (en) | 2009-11-18 | 2016-05-11 | MannKind Corporation | Monoclonal antibodies and diagnostic uses thereof |
| AU2011225577B2 (en) * | 2010-03-11 | 2017-01-19 | Oncotherapy Science, Inc. | HJURP peptides and vaccines including the same |
| US9109007B2 (en) | 2010-08-18 | 2015-08-18 | Purdue Pharma L.P. | MHC-I restricted epitopes containing non-natural amino acid residues |
| CN103124740B (zh) | 2010-09-21 | 2015-09-02 | 美国卫生和人力服务部 | 抗-ssx-2t细胞受体和相关材料及使用方法 |
| RU2615460C2 (ru) | 2010-11-25 | 2017-04-04 | Имнейт Сарл | Иммуногенные пептиды для применения в профилактике и/или лечении инфекционных заболеваний, аутоиммунных заболеваний, иммунных ответов на аллогенные факторы, аллергических заболеваний, опухолей, отторжения трансплантата и иммунных ответов против вирусных векторов. используемых для генной терапии или генной вакцинации |
| WO2012076059A1 (en) * | 2010-12-09 | 2012-06-14 | Stichting Het Nederlands Kanker Instituut | Immune restricted peptides with increased efficacy |
| WO2012088414A1 (en) | 2010-12-23 | 2012-06-28 | Ludwig Institute For Cancer Research Ltd. | Liposomal formulation of nonglycosidic ceramides and uses thereof |
| GB201201511D0 (en) | 2012-01-30 | 2012-03-14 | Univ Leuven Kath | Modified epitopes for boosting CD4+ T-cell responses |
| GB201309469D0 (en) | 2013-05-28 | 2013-07-10 | Imcyse Sa | Detection of CD4+ T lymphocytes |
| US9340799B2 (en) | 2013-09-06 | 2016-05-17 | President And Fellows Of Harvard College | MRNA-sensing switchable gRNAs |
| AU2015298571B2 (en) | 2014-07-30 | 2020-09-03 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
| GB201418433D0 (en) | 2014-10-17 | 2014-12-03 | Imcyse Sa | Novel immunogenic peptides |
| US10729791B2 (en) | 2015-05-18 | 2020-08-04 | Imcyse Sa | Animal models for evaluating pharmaceutical compounds |
| US12043852B2 (en) | 2015-10-23 | 2024-07-23 | President And Fellows Of Harvard College | Evolved Cas9 proteins for gene editing |
| EP3592381A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Cancer vaccine |
| KR20190127797A (ko) | 2017-03-10 | 2019-11-13 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 시토신에서 구아닌으로의 염기 편집제 |
| CN111801345A (zh) | 2017-07-28 | 2020-10-20 | 哈佛大学的校长及成员们 | 使用噬菌体辅助连续进化(pace)的进化碱基编辑器的方法和组合物 |
| EP3724214A4 (en) | 2017-12-15 | 2021-09-01 | The Broad Institute Inc. | SYSTEMS AND METHODS FOR PREDICTING REPAIR RESULTS IN GENETIC ENGINEERING |
| WO2020051566A1 (en) * | 2018-09-07 | 2020-03-12 | Immunotope, Inc. | Vaccines with enhanced immune response and methods for their preparation |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| DE112020001306T5 (de) | 2019-03-19 | 2022-01-27 | Massachusetts Institute Of Technology | Verfahren und zusammensetzungen zur editierung von nukleotidsequenzen |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| IL319653A (en) * | 2022-10-05 | 2025-05-01 | Tscan Therapeutics Inc | Immunogenic PRAME peptides, binding proteins that recognize immunogenic PRAME peptides and uses thereof |
Family Cites Families (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5241047A (en) * | 1988-12-08 | 1993-08-31 | Biochem Pharma Inc. | Synthetic peptides and mixtures thereof for detecting HIV antibodies |
| US5804381A (en) * | 1996-10-03 | 1998-09-08 | Cornell Research Foundation | Isolated nucleic acid molecule encoding an esophageal cancer associated antigen, the antigen itself, and uses thereof |
| US6417165B1 (en) * | 1988-03-27 | 2002-07-09 | Ludwig Institute For Cancer Research | NY-ESO-1-peptide derivatives, and uses thereof |
| DE4128684A1 (de) * | 1991-08-29 | 1993-03-04 | Behringwerke Ag | Hcmv-spezifische peptide, mittel dazu und ihre verwendung |
| US5662907A (en) * | 1992-08-07 | 1997-09-02 | Cytel Corporation | Induction of anti-tumor cytotoxic T lymphocytes in humans using synthetic peptide epitopes |
| EP1757694A3 (en) * | 1992-11-05 | 2008-02-27 | Sloan Kettering Institute For Cancer Research | Prostate-specific membrane antigen |
| US5747271A (en) * | 1992-12-22 | 1998-05-05 | Ludwig Institute For Cancer Research | Method for identifying individuals suffering from a cellular abnormality some of whose abnormal cells present complexes of HLA-A2/tyrosinase derived peptides, and methods for treating said individuals |
| US5620886A (en) * | 1993-03-18 | 1997-04-15 | Ludwig Institute For Cancer Research | Isolated nucleic acid sequence coding for a tumor rejection antigen precursor processed to at least one tumor rejection antigen presented by HLA-A2 |
| US5935818A (en) | 1995-02-24 | 1999-08-10 | Sloan-Kettering Institute For Cancer Research | Isolated nucleic acid molecule encoding alternatively spliced prostate-specific membrane antigen and uses thereof |
| US5874560A (en) | 1994-04-22 | 1999-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Melanoma antigens and their use in diagnostic and therapeutic methods |
| US5830753A (en) | 1994-09-30 | 1998-11-03 | Ludwig Institute For Cancer Research | Isolated nucleic acid molecules coding for tumor rejection antigen precursor dage and uses thereof. |
| US5821122A (en) * | 1995-06-07 | 1998-10-13 | Inserm (Institute Nat'l De La Sante Et De La Recherche . .) | Isolated nucleic acid molecules, peptides which form complexes with MHC molecule HLA-A2 and uses thereof |
| US6025191A (en) * | 1995-06-07 | 2000-02-15 | Ludwig Institute For Cancer Research | Isolated nucleic acid molecules which encode a melanoma specific antigen and uses thereof |
| US6548064B1 (en) * | 1997-05-05 | 2003-04-15 | Ludwig Institute For Cancer Research | Isolated peptides consisting of amino acid sequences found in SSX or NY-ESO-1 molecules, which bind to HLA molecules |
| US6025470A (en) * | 1997-06-23 | 2000-02-15 | Ludwig Institute For Cancer Research | Isolated nona- and decapeptides which bind to HLA molecules, and the use thereof |
| US6977074B2 (en) * | 1997-07-10 | 2005-12-20 | Mannkind Corporation | Method of inducing a CTL response |
| US6994851B1 (en) * | 1997-07-10 | 2006-02-07 | Mannkind Corporation | Method of inducing a CTL response |
| IL133912A0 (en) | 1997-07-10 | 2001-04-30 | Ctl Immunotherapies Corp | A method of inducing ctl response |
| US6576755B1 (en) * | 1997-09-10 | 2003-06-10 | Zymogenetics, Inc. | Beta-defensins |
| US20030138808A1 (en) | 1998-02-19 | 2003-07-24 | Simard John J.L. | Expression vectors encoding epitopes of target-associated antigens |
| US6709844B1 (en) * | 2000-11-16 | 2004-03-23 | Mannkind Corporation | Avoidance of undesirable replication intermediates in plasmid propagation |
| US20020072493A1 (en) | 1998-05-19 | 2002-06-13 | Yeda Research And Development Co. Ltd. | Activated T cells, nervous system-specific antigens and their uses |
| US6777388B1 (en) * | 1998-08-21 | 2004-08-17 | Clf Medical Technology Acceleration Program, Inc. | Leptin-related peptides |
| GB9818938D0 (en) * | 1998-08-28 | 1998-10-21 | Alpharma As | Bioactive peptides |
| NZ513482A (en) | 1999-02-05 | 2003-08-29 | Univ Melbourne | T helper cell epitodes derived from canine distemper virus for producing an immune response in an animal |
| US7157091B1 (en) * | 1999-06-18 | 2007-01-02 | Ludwig Institute For Cancer Research | MAGE-A1 peptides presented by HLA class II molecules |
| EA004739B1 (ru) * | 1999-11-05 | 2004-08-26 | Эксоникс, Инк. | ПЕПТИДНЫЕ АНАЛОГИ И МИМЕТИКИ, ПОДХОДЯЩИЕ ДЛЯ ПРИМЕНЕНИЯ IN VIVO ПРИ ЛЕЧЕНИИ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С АНОМАЛЬНОЙ УКЛАДКОЙ БЕЛКОВ В АМИЛОИДНЫЕ ИЛИ АМИЛОИДПОДОБНЫЕ ОТЛОЖЕНИЯ, ИЛИ ИХ ПАТОЛОГИЧЕСКИЕ ПРЕДШЕСТВЕННИКИ, ОБОГАЩЕННЫЕ b-СКЛАДКАМИ |
| JP4615805B2 (ja) * | 1999-11-15 | 2011-01-19 | ルードヴィッヒ インスティテュート フォー キャンサー リサーチ | Ny−eso−1ペプチド誘導体およびその使用 |
| US6605711B1 (en) * | 1999-11-15 | 2003-08-12 | Ludwig Institute For Cancer Research | NY-ESO-1 peptide derivatives, and uses thereof |
| CA2386341A1 (en) * | 1999-11-18 | 2001-05-25 | Epimmune Inc. | Heteroclitic analogs and related methods |
| EP1118860A1 (en) | 2000-01-21 | 2001-07-25 | Rijksuniversiteit te Leiden | Methods for selecting and producing T cell peptide epitopes and vaccines incorporating said selected epitopes |
| WO2001062776A1 (en) | 2000-02-23 | 2001-08-30 | Epimmune Inc. | Hla binding peptides and their uses |
| CA2405568A1 (en) * | 2000-04-05 | 2001-10-18 | North Carolina State University | Prion-binding peptidic ligands and methods of using same |
| US20030215425A1 (en) * | 2001-12-07 | 2003-11-20 | Simard John J. L. | Epitope synchronization in antigen presenting cells |
| US6861234B1 (en) * | 2000-04-28 | 2005-03-01 | Mannkind Corporation | Method of epitope discovery |
| EP1372736A4 (en) | 2001-03-07 | 2004-11-17 | Mannkind Corp | PREPARATIONS AGAINST CANCER FORMATION |
| WO2003008537A2 (en) | 2001-04-06 | 2003-01-30 | Mannkind Corporation | Epitope sequences |
| US20030148973A1 (en) * | 2001-05-23 | 2003-08-07 | Peter Emtage | MAGE-A1 peptides for treating or preventing cancer |
| US20030017134A1 (en) * | 2001-06-19 | 2003-01-23 | Technion Research And Development Foundation Ltd. | Methods and pharmaceutical compositions for immune deception, particularly useful in the treatment of cancer |
| CN101024842A (zh) | 2001-11-07 | 2007-08-29 | 曼康公司 | 编码靶相关抗原表位的表达载体及其设计方法 |
| US20060128607A1 (en) * | 2002-01-29 | 2006-06-15 | Anja-Katrin Bosserhoff | Method for inhibiting "melanoma inhibitory activity" mia |
| US6992176B2 (en) * | 2002-02-13 | 2006-01-31 | Technion Research & Development Foundation Ltd. | Antibody having a T-cell receptor-like specificity, yet higher affinity, and the use of same in the detection and treatment of cancer, viral infection and autoimmune disease |
| US8802618B2 (en) | 2002-03-08 | 2014-08-12 | Board Of Regents, The University Of Texas System | Controlled modulation of amino acid side chain length of peptide antigens |
| US7563882B2 (en) * | 2002-06-10 | 2009-07-21 | University Of Rochester | Polynucleotides encoding antibodies that bind to the C35 polypeptide |
| US20070105779A1 (en) * | 2002-07-31 | 2007-05-10 | Danila Valmori | Isolated, ssx-2 and ssx-2 related peptides useful as hla binders and ctl epitopes, and uses thereof |
| US7906620B2 (en) | 2002-08-16 | 2011-03-15 | Yeda Research And Development Co. Ltd. | Tumor associated antigen, peptides thereof, and use of same as anti-tumor vaccines |
| CN1691964A (zh) | 2002-09-06 | 2005-11-02 | 曼康公司 | 表位序列 |
| EP1556072B1 (en) * | 2002-09-17 | 2010-05-19 | Antigen Express, Inc. | Ii-KEY/ANTIGENIC EPITOPE HYBRID PEPTIDE VACCINES |
| ATE546153T1 (de) * | 2003-06-17 | 2012-03-15 | Mannkind Corp | Kombinationen von tumor-assoziierten antigenen zur behandlung von verschiedenen krebstypen |
| MXPA05013973A (es) | 2003-06-17 | 2006-03-02 | Mannkind Corp | Metodos para producir, mejorar y sustentar respuestas inmunes contra epitopes restringidos mhc clase i, para propositos profilacticos o terapeuticos. |
| JP2008503494A (ja) | 2004-06-17 | 2008-02-07 | マンカインド コーポレイション | 診断方法を治療方法と統合することによる免疫療法の効力改善 |
| US20060159689A1 (en) | 2004-06-17 | 2006-07-20 | Chih-Sheng Chiang | Combinations of tumor-associated antigens in diagnostics for various types of cancers |
| EP2332971B1 (en) | 2004-06-17 | 2016-02-17 | MannKind Corporation | Epitope analogs |
| US20060008468A1 (en) * | 2004-06-17 | 2006-01-12 | Chih-Sheng Chiang | Combinations of tumor-associated antigens in diagnostics for various types of cancers |
| AU2005321898B2 (en) * | 2004-12-29 | 2012-07-19 | Mannkind Corporation | Use of compositions comprising various tumor-associated antigens as anti-cancer vaccines |
| KR101294290B1 (ko) * | 2004-12-29 | 2013-08-07 | 맨카인드 코포레이션 | 예방 또는 치료를 위해 제i류 주조직 적합성복합체〔mhc〕-제한 에피토프에 대한 면역 반응을 유발,향상 및 지속하는 방법 |
| EP2351576A1 (en) | 2004-12-29 | 2011-08-03 | Mannkind Corporation | Methods to trigger, maintain and manipulate immune responses by targeted administration of biological response modifiers into lymphoid organs |
| US9469902B2 (en) | 2014-02-18 | 2016-10-18 | Lam Research Corporation | Electroless deposition of continuous platinum layer |
| EP3636238B1 (en) | 2018-10-12 | 2021-04-28 | Liko Research & Development AB | Gates with transition ramps for overhead lifting rails |
-
2005
- 2005-06-17 EP EP10180780.8A patent/EP2332971B1/en not_active Expired - Lifetime
- 2005-06-17 AU AU2005265182A patent/AU2005265182B2/en not_active Ceased
- 2005-06-17 SG SG200904127-8A patent/SG153827A1/en unknown
- 2005-06-17 WO PCT/US2005/021609 patent/WO2006009920A2/en not_active Ceased
- 2005-06-17 MX MXPA06014768A patent/MXPA06014768A/es active IP Right Grant
- 2005-06-17 US US11/155,929 patent/US8354380B2/en not_active Expired - Fee Related
- 2005-06-17 US US11/156,253 patent/US8202841B2/en not_active Expired - Fee Related
- 2005-06-17 US US11/156,369 patent/US20060057673A1/en not_active Abandoned
- 2005-06-17 JP JP2007516810A patent/JP5166025B2/ja not_active Expired - Fee Related
- 2005-06-17 CA CA002571168A patent/CA2571168A1/en not_active Abandoned
- 2005-06-17 KR KR1020077001143A patent/KR20070056042A/ko not_active Ceased
- 2005-06-17 EP EP05762506A patent/EP1765858B1/en not_active Expired - Lifetime
- 2005-06-17 KR KR1020107013889A patent/KR20100092031A/ko not_active Ceased
-
2006
- 2006-12-14 IL IL180101A patent/IL180101A/en not_active IP Right Cessation
-
2008
- 2008-06-13 JP JP2008155749A patent/JP2008283979A/ja not_active Ceased
-
2010
- 2010-12-09 IL IL209859A patent/IL209859A0/en unknown
-
2011
- 2011-02-28 US US13/037,350 patent/US20110301327A1/en not_active Abandoned
-
2013
- 2013-01-14 US US13/741,232 patent/US20130195901A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2008283979A (ja) | 2008-11-27 |
| EP2332971A1 (en) | 2011-06-15 |
| IL180101A (en) | 2014-02-27 |
| SG153827A1 (en) | 2009-07-29 |
| US20060094661A1 (en) | 2006-05-04 |
| KR20070056042A (ko) | 2007-05-31 |
| AU2005265182A1 (en) | 2006-01-26 |
| EP2332971B1 (en) | 2016-02-17 |
| CA2571168A1 (en) | 2006-01-26 |
| US20130195901A1 (en) | 2013-08-01 |
| US8202841B2 (en) | 2012-06-19 |
| EP1765858A2 (en) | 2007-03-28 |
| JP2008510453A (ja) | 2008-04-10 |
| WO2006009920A2 (en) | 2006-01-26 |
| US20110301327A1 (en) | 2011-12-08 |
| US20060057673A1 (en) | 2006-03-16 |
| US20060063913A1 (en) | 2006-03-23 |
| IL180101A0 (en) | 2007-05-15 |
| EP1765858B1 (en) | 2012-11-21 |
| KR20100092031A (ko) | 2010-08-19 |
| AU2005265182B2 (en) | 2012-06-21 |
| IL209859A0 (en) | 2011-02-28 |
| MXPA06014768A (es) | 2007-06-22 |
| WO2006009920A3 (en) | 2006-06-15 |
| US8354380B2 (en) | 2013-01-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5166025B2 (ja) | エピトープアナログ | |
| US7605227B2 (en) | Melanoma antigen peptide analogues | |
| CN101001868A (zh) | 表位类似物 | |
| NZ583226A (en) | Epitope analogs | |
| AU2013201661A1 (en) | Epitope Analogues | |
| HK1122823A (en) | Epitope analogues | |
| HK1163116A (en) | Epitope analogues | |
| HK1163115A (en) | Epitope analogues | |
| HK1159124A (en) | Epitope analogs | |
| HK1163117A (en) | Epitope analogues |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080613 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080613 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110222 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110523 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110530 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110621 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110628 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110721 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110728 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110822 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111206 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120306 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120313 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120406 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120413 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120501 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120510 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120606 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20121204 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20121220 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20151228 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110822 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |