JP2002534083A - 骨髄機能廃絶性ではない寛容原性の処置 - Google Patents
骨髄機能廃絶性ではない寛容原性の処置Info
- Publication number
- JP2002534083A JP2002534083A JP2000592399A JP2000592399A JP2002534083A JP 2002534083 A JP2002534083 A JP 2002534083A JP 2000592399 A JP2000592399 A JP 2000592399A JP 2000592399 A JP2000592399 A JP 2000592399A JP 2002534083 A JP2002534083 A JP 2002534083A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- donor
- mammal
- host
- mice
- 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
- 238000011282 treatment Methods 0.000 title claims abstract description 76
- 230000001400 myeloablative effect Effects 0.000 title claims abstract description 45
- 230000003614 tolerogenic effect Effects 0.000 title abstract description 48
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 173
- 241000124008 Mammalia Species 0.000 claims abstract description 138
- 239000000427 antigen Substances 0.000 claims abstract description 119
- 108091007433 antigens Proteins 0.000 claims abstract description 119
- 102000036639 antigens Human genes 0.000 claims abstract description 119
- 210000004698 lymphocyte Anatomy 0.000 claims abstract description 113
- 238000000034 method Methods 0.000 claims abstract description 104
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims abstract description 87
- 210000001185 bone marrow Anatomy 0.000 claims abstract description 51
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 26
- 239000003018 immunosuppressive agent Substances 0.000 claims abstract description 18
- 230000001472 cytotoxic effect Effects 0.000 claims abstract description 17
- 231100000433 cytotoxic Toxicity 0.000 claims abstract description 16
- 230000008030 elimination Effects 0.000 claims abstract description 12
- 238000003379 elimination reaction Methods 0.000 claims abstract description 12
- 230000001939 inductive effect Effects 0.000 claims abstract description 12
- 229940125721 immunosuppressive agent Drugs 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 285
- 239000000203 mixture Substances 0.000 claims description 58
- 206010028980 Neoplasm Diseases 0.000 claims description 57
- 238000000338 in vitro Methods 0.000 claims description 38
- 210000001519 tissue Anatomy 0.000 claims description 37
- 201000011510 cancer Diseases 0.000 claims description 36
- 210000000056 organ Anatomy 0.000 claims description 33
- 241001465754 Metazoa Species 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 30
- 238000002659 cell therapy Methods 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 239000005022 packaging material Substances 0.000 claims description 16
- 230000001413 cellular effect Effects 0.000 claims description 15
- 230000000779 depleting effect Effects 0.000 claims description 12
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 10
- 230000004043 responsiveness Effects 0.000 claims description 10
- 230000001861 immunosuppressant effect Effects 0.000 claims description 7
- PBUUPFTVAPUWDE-UGZDLDLSSA-N 2-[[(2S,4S)-2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2lambda5-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonic acid Chemical compound OS(=O)(=O)CCS[C@H]1CCO[P@](=O)(N(CCCl)CCCl)N1 PBUUPFTVAPUWDE-UGZDLDLSSA-N 0.000 claims description 3
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims description 3
- 229950000547 mafosfamide Drugs 0.000 claims description 3
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims description 3
- 238000002054 transplantation Methods 0.000 abstract description 56
- 239000000463 material Substances 0.000 abstract description 17
- 241000699670 Mus sp. Species 0.000 description 210
- 210000004989 spleen cell Anatomy 0.000 description 165
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 92
- 208000024908 graft versus host disease Diseases 0.000 description 90
- 208000009329 Graft vs Host Disease Diseases 0.000 description 81
- 210000002798 bone marrow cell Anatomy 0.000 description 69
- 210000003491 skin Anatomy 0.000 description 63
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 55
- 101000980756 Homo sapiens G1/S-specific cyclin-D1 Proteins 0.000 description 55
- 230000000735 allogeneic effect Effects 0.000 description 54
- 230000000694 effects Effects 0.000 description 51
- 238000002347 injection Methods 0.000 description 41
- 239000007924 injection Substances 0.000 description 41
- 210000000130 stem cell Anatomy 0.000 description 40
- 210000004369 blood Anatomy 0.000 description 34
- 239000008280 blood Substances 0.000 description 34
- 241000699666 Mus <mouse, genus> Species 0.000 description 30
- 210000004881 tumor cell Anatomy 0.000 description 30
- 102000004127 Cytokines Human genes 0.000 description 26
- 108090000695 Cytokines Proteins 0.000 description 26
- 238000002474 experimental method Methods 0.000 description 25
- 208000032839 leukemia Diseases 0.000 description 25
- 239000006228 supernatant Substances 0.000 description 24
- 230000003394 haemopoietic effect Effects 0.000 description 23
- 206010068051 Chimerism Diseases 0.000 description 21
- 230000004083 survival effect Effects 0.000 description 21
- 102000000588 Interleukin-2 Human genes 0.000 description 19
- 108010002350 Interleukin-2 Proteins 0.000 description 19
- 230000001506 immunosuppresive effect Effects 0.000 description 17
- 210000000952 spleen Anatomy 0.000 description 17
- 210000002216 heart Anatomy 0.000 description 16
- 230000004044 response Effects 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 15
- 230000006698 induction Effects 0.000 description 14
- 230000035899 viability Effects 0.000 description 14
- 238000011129 allogeneic cell therapy Methods 0.000 description 13
- 230000008901 benefit Effects 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 238000002649 immunization Methods 0.000 description 13
- 238000001802 infusion Methods 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 238000012546 transfer Methods 0.000 description 13
- 230000003053 immunization Effects 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 12
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 12
- 241000282412 Homo Species 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 238000011081 inoculation Methods 0.000 description 11
- 241000282887 Suidae Species 0.000 description 10
- 210000000601 blood cell Anatomy 0.000 description 10
- 210000000822 natural killer cell Anatomy 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 108010074328 Interferon-gamma Proteins 0.000 description 9
- 230000000890 antigenic effect Effects 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000004888 barrier function Effects 0.000 description 9
- 230000009089 cytolysis Effects 0.000 description 9
- 210000000265 leukocyte Anatomy 0.000 description 9
- 206010052804 Drug tolerance Diseases 0.000 description 8
- 206010062016 Immunosuppression Diseases 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000026781 habituation Effects 0.000 description 8
- 241000894007 species Species 0.000 description 8
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 7
- 102000003814 Interleukin-10 Human genes 0.000 description 7
- 108090000174 Interleukin-10 Proteins 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 241000282898 Sus scrofa Species 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 7
- 210000000988 bone and bone Anatomy 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- 239000012636 effector Substances 0.000 description 7
- 230000036039 immunity Effects 0.000 description 7
- 229940076144 interleukin-10 Drugs 0.000 description 7
- 231100000518 lethal Toxicity 0.000 description 7
- 230000001665 lethal effect Effects 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 230000003211 malignant effect Effects 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000009257 reactivity Effects 0.000 description 7
- 102100037850 Interferon gamma Human genes 0.000 description 6
- 102000004388 Interleukin-4 Human genes 0.000 description 6
- 108090000978 Interleukin-4 Proteins 0.000 description 6
- 230000000961 alloantigen Effects 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 230000028993 immune response Effects 0.000 description 6
- 229940028885 interleukin-4 Drugs 0.000 description 6
- 230000007774 longterm Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 210000005259 peripheral blood Anatomy 0.000 description 6
- 239000011886 peripheral blood Substances 0.000 description 6
- 238000003752 polymerase chain reaction Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 5
- 208000017604 Hodgkin disease Diseases 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 206010037660 Pyrexia Diseases 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 210000000612 antigen-presenting cell Anatomy 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000012258 culturing Methods 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 239000012678 infectious agent Substances 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 230000005865 ionizing radiation Effects 0.000 description 5
- 238000011694 lewis rat Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 108010062580 Concanavalin A Proteins 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 4
- 101001100327 Homo sapiens RNA-binding protein 45 Proteins 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 102000043129 MHC class I family Human genes 0.000 description 4
- 108091054437 MHC class I family Proteins 0.000 description 4
- 108010047620 Phytohemagglutinins Proteins 0.000 description 4
- 102100038823 RNA-binding protein 45 Human genes 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 206010052779 Transplant rejections Diseases 0.000 description 4
- 230000006978 adaptation Effects 0.000 description 4
- 238000011316 allogeneic transplantation Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 230000003750 conditioning effect Effects 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 239000003226 mitogen Substances 0.000 description 4
- 230000001885 phytohemagglutinin Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
- 101100284398 Bos taurus BoLA-DQB gene Proteins 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 3
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 101000981253 Mus musculus GPI-linked NAD(P)(+)-arginine ADP-ribosyltransferase 1 Proteins 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- 206010033661 Pancytopenia Diseases 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 238000010322 bone marrow transplantation Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229960004397 cyclophosphamide Drugs 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 210000004700 fetal blood Anatomy 0.000 description 3
- 208000016361 genetic disease Diseases 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 210000000689 upper leg Anatomy 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 238000002689 xenotransplantation Methods 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 208000032467 Aplastic anaemia Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000004736 B-Cell Leukemia Diseases 0.000 description 2
- 208000003950 B-cell lymphoma Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010010144 Completed suicide Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 206010012735 Diarrhoea Diseases 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
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 229940126530 T cell activator Drugs 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 101150052863 THY1 gene Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 230000004940 costimulation Effects 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000002565 electrocardiography Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 210000000604 fetal stem cell Anatomy 0.000 description 2
- 229960000390 fludarabine Drugs 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 210000000777 hematopoietic system Anatomy 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000007813 immunodeficiency Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 229940124589 immunosuppressive drug Drugs 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 229940117681 interleukin-12 Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000004153 islets of langerhan Anatomy 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 210000004324 lymphatic system Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 230000015654 memory Effects 0.000 description 2
- 230000003818 metabolic dysfunction Effects 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000008775 paternal effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 210000004976 peripheral blood cell Anatomy 0.000 description 2
- 230000003836 peripheral circulation Effects 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000011476 stem cell transplantation Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 241001132374 Asta Species 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 102100033779 Collagen alpha-4(IV) chain Human genes 0.000 description 1
- 235000006481 Colocasia esculenta Nutrition 0.000 description 1
- 240000004270 Colocasia esculenta var. antiquorum Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 208000015872 Gaucher disease Diseases 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
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 1
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 1
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 1
- 108010075704 HLA-A Antigens Proteins 0.000 description 1
- 108010058607 HLA-B Antigens Proteins 0.000 description 1
- 108010052199 HLA-C Antigens Proteins 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 101000710870 Homo sapiens Collagen alpha-4(IV) chain Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 206010069360 Leukaemic infiltration Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025280 Lymphocytosis Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 101150076359 Mhc gene Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 1
- 229960004821 amikacin Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002942 anti-growth Effects 0.000 description 1
- 230000000919 anti-host Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- 230000000781 anti-lymphocytic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001494 anti-thymocyte effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940063123 diflucan Drugs 0.000 description 1
- 208000029640 digestive system melanoma Diseases 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 101150008103 hal gene Proteins 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000009033 hematopoietic malignancy Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000006054 immunological memory Effects 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 230000006057 immunotolerant effect Effects 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004073 interleukin-2 production Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000036546 leukodystrophy Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000036473 myasthenia Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 208000002865 osteopetrosis Diseases 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000004214 philadelphia chromosome Anatomy 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 210000000614 rib Anatomy 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- 208000011571 secondary malignant neoplasm Diseases 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- GFWRVVCDTLRWPK-KPKJPENVSA-N sofalcone Chemical compound C1=CC(OCC=C(C)C)=CC=C1\C=C\C(=O)C1=CC=C(OCC=C(C)C)C=C1OCC(O)=O GFWRVVCDTLRWPK-KPKJPENVSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000007801 sublethal irradiation Methods 0.000 description 1
- FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- -1 tazosin Chemical compound 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 230000024664 tolerance induction Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000011131 xenogeneic cell therapy Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0271—Chimeric vertebrates, e.g. comprising exogenous cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/001—Preparations to induce tolerance to non-self, e.g. prior to transplantation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
- A61K40/22—Immunosuppressive or immunotolerising
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/418—Antigens related to induction of tolerance to non-self
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
- A61K2239/48—Blood cells, e.g. leukemia or lymphoma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/50—Cellular immunotherapy characterised by the use of allogeneic cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Developmental Biology & Embryology (AREA)
- Transplantation (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Husbandry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/222,011 | 1998-12-31 | ||
| US09/222,011 US6428782B1 (en) | 1997-05-23 | 1998-12-31 | Non-myeloablative tolerogenic treatment |
| PCT/US1999/030704 WO2000040701A2 (en) | 1998-12-31 | 1999-12-23 | Non-myeloablative tolerogenic treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002534083A true JP2002534083A (ja) | 2002-10-15 |
| JP2002534083A5 JP2002534083A5 (enExample) | 2007-02-22 |
Family
ID=22830367
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000592399A Pending JP2002534083A (ja) | 1998-12-31 | 1999-12-23 | 骨髄機能廃絶性ではない寛容原性の処置 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6428782B1 (enExample) |
| EP (3) | EP1141246A2 (enExample) |
| JP (1) | JP2002534083A (enExample) |
| CA (1) | CA2356434A1 (enExample) |
| IL (1) | IL143485A0 (enExample) |
| WO (1) | WO2000040701A2 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL140796A0 (en) * | 2001-01-08 | 2002-02-10 | Hadasit Med Res Service | An autologous anti-cancer vaccine |
| JP3734461B2 (ja) | 2001-08-08 | 2006-01-11 | 松下電器産業株式会社 | ライセンス情報変換装置 |
| WO2003038048A2 (en) * | 2001-10-30 | 2003-05-08 | The United States Of America As Represented By The Secretary Of The Navy | Ex-vivo rescue of transplantable hematopoietic stem cells following myeloablative injury |
| AU2002952834A0 (en) * | 2002-09-16 | 2002-12-05 | The Walter And Eliza Hall Institute Of Medical Research | A method of treating an autoimmune disease |
| WO2005021734A2 (en) * | 2003-09-02 | 2005-03-10 | University Of Massachussets | Generation of hematopoietic chimerism and induction of central tolerance |
| MX2008000974A (es) * | 2005-07-22 | 2008-03-27 | Univ California | Composiciones de heparina e inhibicion de selectina. |
| EP2345412A1 (en) * | 2005-12-02 | 2011-07-20 | The Johns Hopkins University | Use of high-dose oxazaphosphorine drugs for treating immune disorders |
| WO2008034076A2 (en) | 2006-09-15 | 2008-03-20 | The Johns Hopkins University | Cyclophosphamide in combination with immune therapeutics |
| WO2008034071A2 (en) | 2006-09-15 | 2008-03-20 | The Johns Hopkins University | Method of identifying patients suitable for high-dose cyclophosphamide treatment |
| WO2008034074A2 (en) | 2006-09-15 | 2008-03-20 | The Johns Hopkins University | Cyclosphosphamide in combination with anti-idiotypic vaccines |
| US9026372B2 (en) * | 2007-11-21 | 2015-05-05 | Accentia Biopharmaceuticals, Inc. | Methods for providing a system of care for a high-dose oxazaphosphorine drug regimen |
| WO2009067690A2 (en) * | 2007-11-21 | 2009-05-28 | Accentia Biopharmaceuticals, Inc. | Methods for safe and effective treatment using oxazaphosphorine drugs |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09510456A (ja) * | 1994-03-17 | 1997-10-21 | バクスター、インターナショナル、インコーポレイテッド | 同種リンパ球による癌の免疫療法 |
| WO1998020932A2 (en) * | 1996-11-15 | 1998-05-22 | Baxter International Inc. | Conditioning for allogeneic stem cell transplantation |
| WO1998052582A2 (en) * | 1997-05-23 | 1998-11-26 | Hadasit Medical Research Services And Development Ltd. | Non-myeloablative tolerogenic treatment |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5273738A (en) | 1990-03-03 | 1993-12-28 | Fred Hutchinson Cancer Research Center | Radiation delivery to lymphoid and marrow tissues |
| PT621786E (pt) | 1992-01-08 | 2002-07-31 | Gen Hospital Corp | Inducao da tolerancia a xenoenxertos |
| US5876708A (en) | 1992-02-19 | 1999-03-02 | The General Hospital Corporation | Allogeneic and xenogeneic transplantation |
| US5589582A (en) | 1992-10-27 | 1996-12-31 | Biotransplant, Inc. | Polynucleotides en coding porcine cytokines |
| AU7404494A (en) | 1993-07-21 | 1995-02-20 | Cellpro, Incorporated | Methods and compositions for preventing immune rejection of solid organ grafts |
| ATE188487T1 (de) * | 1993-09-02 | 2000-01-15 | Dartmouth College | Anti-gp39 antikoerper und deren verwendungen |
| US5635156A (en) | 1993-09-13 | 1997-06-03 | University Of Pittsburgh | Non-lethal methods for conditioning a recipient for bone marrow transplantation |
| US5514364A (en) | 1993-09-13 | 1996-05-07 | University Of Pittsburgh | Non-lethal methods for conditioning a recipient for bone marrow transplantation |
| WO1996031229A1 (en) * | 1995-04-05 | 1996-10-10 | Beth Israel Hospital Association | Inhibiting rejection of a graft |
| WO1996037208A1 (en) | 1995-05-25 | 1996-11-28 | Baxter International Inc. | Allogeneic cell therapy for cancer following allogeneic stem cell transplantation |
-
1998
- 1998-12-31 US US09/222,011 patent/US6428782B1/en not_active Expired - Lifetime
-
1999
- 1999-12-23 CA CA002356434A patent/CA2356434A1/en not_active Abandoned
- 1999-12-23 WO PCT/US1999/030704 patent/WO2000040701A2/en not_active Ceased
- 1999-12-23 IL IL14348599A patent/IL143485A0/xx not_active IP Right Cessation
- 1999-12-23 EP EP99968946A patent/EP1141246A2/en not_active Withdrawn
- 1999-12-23 EP EP04024995A patent/EP1498136A2/en not_active Withdrawn
- 1999-12-23 EP EP04024994A patent/EP1498479A2/en not_active Withdrawn
- 1999-12-23 JP JP2000592399A patent/JP2002534083A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09510456A (ja) * | 1994-03-17 | 1997-10-21 | バクスター、インターナショナル、インコーポレイテッド | 同種リンパ球による癌の免疫療法 |
| WO1998020932A2 (en) * | 1996-11-15 | 1998-05-22 | Baxter International Inc. | Conditioning for allogeneic stem cell transplantation |
| WO1998052582A2 (en) * | 1997-05-23 | 1998-11-26 | Hadasit Medical Research Services And Development Ltd. | Non-myeloablative tolerogenic treatment |
Non-Patent Citations (1)
| Title |
|---|
| JPN6010001581, 今日の移植(1992),Vol.5,No.3,p.317−322 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1498136A8 (en) | 2005-04-13 |
| WO2000040701A9 (en) | 2001-09-13 |
| WO2000040701A3 (en) | 2000-12-21 |
| US6428782B1 (en) | 2002-08-06 |
| EP1498479A2 (en) | 2005-01-19 |
| CA2356434A1 (en) | 2000-07-13 |
| EP1498136A2 (en) | 2005-01-19 |
| EP1141246A2 (en) | 2001-10-10 |
| WO2000040701A2 (en) | 2000-07-13 |
| IL143485A0 (en) | 2002-04-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pelot et al. | Lymphohematopoietic graft-vs.-host reactions can be induced without graft-vs.-host disease in murine mixed chimeras established with a cyclophosphamide-based nonmyeloablative conditioning regimen | |
| US6877514B2 (en) | Mixed chimerism and tolerance | |
| US8734786B2 (en) | Use of ECDI-fixed cell tolerance as a method for preventing allograft rejection | |
| Mehta et al. | Graft-versus-myeloma | |
| US20150104471A1 (en) | Universal donor-derived tolerogenic cells for inducing non-syngeneic transplantation tolerance | |
| Mapara et al. | Donor lymphocyte infusion-mediated graft-versus-leukemia effects in mixed chimeras established with a nonmyeloablative conditioning regimen: extinction of graft-versus-leukemia effects after conversion to full donor chimerism1 | |
| HARDY et al. | Pancreatic islet transplantation: induction of graft acceptance by ultraviolet irradiation of donor tissue | |
| US6428782B1 (en) | Non-myeloablative tolerogenic treatment | |
| US6447767B1 (en) | Non-myeloablative tolerogenic treatment | |
| Gibbons et al. | Manipulating the immune system for anti‐tumor responses and transplant tolerance via mixed hematopoietic chimerism | |
| Sykes | Mechanisms of tolerance | |
| Yin et al. | Allograft tolerance induced by intact active bone co-transplantation and anti-CD40L monoclonal antibody therapy1 | |
| US20060140912A9 (en) | Methods for enhancing engraftment of purified hematopoietic stem cells in allogeneic recipients | |
| EP0983074B1 (en) | Non-myeloablative tolerogenic treatment | |
| Cutler et al. | Neonatally tolerant rats actively eliminate donor‐specific lymphocytes despite persistent chimerism | |
| JP3553941B2 (ja) | 異種移植片の胸腺 | |
| WO1995021527A1 (en) | Stem cell engraftment | |
| EP0249502A2 (en) | Soluble immune suppressor factor and suppressor cells | |
| Martin et al. | Engraftment, Graft Rejection, and Graft Failure | |
| Hall et al. | Transplant Tolerance | |
| Davenport et al. | The role of the facilitating cell in the establishment of donor chimerism and transplantation tolerance | |
| Gatti et al. | History of hematopoietic stem cell transplantation | |
| Olivares-Villagomez | Control of autoimmune encephalomyelitis by CD4+ T cell receptor alpha-beta+ lymphocytes and their role in T cell homeostasis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20061221 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061221 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100115 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100611 |