JP2014527398A

JP2014527398A - がんの療法および診断のための組成物および方法

がんの療法および診断のための組成物および方法 Download PDF

Info

Publication number: JP2014527398A
Authority: JP; Japan
Prior art keywords: seq; cancer; polypeptide; sequence; antigen
Prior art date: 2011-06-21
Legal status : Pending

Application number

JP2014517079A

Other languages

English (en)

Japanese (ja)

Other versions

JP2014527398A5 (enExample

Inventor

サラエレンウォレン，

カールワイズマン，

Original Assignee

オンコファクターコーポレイション

Priority date

2011-06-21

Filing date

2012-06-19

Publication date

2014-10-16

2012-06-19 Application filed by オンコファクターコーポレイション, オンコファクターコーポレイション filed Critical オンコファクターコーポレイション

2014-10-16 Publication of JP2014527398A publication Critical patent/JP2014527398A/ja

2015-07-30 Publication of JP2014527398A5 publication Critical patent/JP2014527398A5/ja

Status Pending legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 176
239000000203 mixture Substances 0.000 title claims abstract description 140
238000003745 diagnosis Methods 0.000 title abstract description 9
238000011275 oncology therapy Methods 0.000 title abstract description 5
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 319
102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 301
229920001184 polypeptide Polymers 0.000 claims abstract description 292
206010028980 Neoplasm Diseases 0.000 claims abstract description 263
201000011510 cancer Diseases 0.000 claims abstract description 188
102000040430 polynucleotide Human genes 0.000 claims abstract description 130
108091033319 polynucleotide Proteins 0.000 claims abstract description 130
239000002157 polynucleotide Substances 0.000 claims abstract description 130
230000027455 binding Effects 0.000 claims abstract description 108
239000000427 antigen Substances 0.000 claims abstract description 90
108091007433 antigens Proteins 0.000 claims abstract description 90
102000036639 antigens Human genes 0.000 claims abstract description 90
239000012634 fragment Substances 0.000 claims abstract description 89
238000011282 treatment Methods 0.000 claims abstract description 18
239000000523 sample Substances 0.000 claims description 71
125000003275 alpha amino acid group Chemical group 0.000 claims description 45
239000008194 pharmaceutical composition Substances 0.000 claims description 42
108091034117 Oligonucleotide Proteins 0.000 claims description 39
239000002158 endotoxin Substances 0.000 claims description 31
230000000295 complement effect Effects 0.000 claims description 30
238000001514 detection method Methods 0.000 claims description 30
206010006187 Breast cancer Diseases 0.000 claims description 29
208000026310 Breast neoplasm Diseases 0.000 claims description 29
239000012472 biological sample Substances 0.000 claims description 29
101000960952 Homo sapiens Interleukin-1 receptor accessory protein Proteins 0.000 claims description 24
102100039880 Interleukin-1 receptor accessory protein Human genes 0.000 claims description 24
101000978381 Homo sapiens C-C motif chemokine 14 Proteins 0.000 claims description 23
102100023705 C-C motif chemokine 14 Human genes 0.000 claims description 21
102100021245 G-protein coupled receptor 183 Human genes 0.000 claims description 21
101001040801 Homo sapiens G-protein coupled receptor 183 Proteins 0.000 claims description 21
108010029485 Protein Isoforms Proteins 0.000 claims description 21
102000001708 Protein Isoforms Human genes 0.000 claims description 21
SIVJKYRAPQKLIM-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-n-(3-fluoro-5-morpholin-4-ylphenyl)propanamide Chemical compound C=1C(N2CCOCC2)=CC(F)=CC=1NC(=O)CCC1=CC=C(F)C(F)=C1 SIVJKYRAPQKLIM-UHFFFAOYSA-N 0.000 claims description 20
101001076422 Homo sapiens Interleukin-1 receptor type 2 Proteins 0.000 claims description 20
102100026017 Interleukin-1 receptor type 2 Human genes 0.000 claims description 20
239000003153 chemical reaction reagent Substances 0.000 claims description 20
208000020816 lung neoplasm Diseases 0.000 claims description 19
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 17
201000005202 lung cancer Diseases 0.000 claims description 17
108010056102 CD100 antigen Proteins 0.000 claims description 15
102100027744 Semaphorin-4D Human genes 0.000 claims description 15
239000003937 drug carrier Substances 0.000 claims description 13
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 10
102100022718 Atypical chemokine receptor 2 Human genes 0.000 claims description 10
102100026194 C-type lectin domain family 2 member B Human genes 0.000 claims description 10
102100037084 C4b-binding protein alpha chain Human genes 0.000 claims description 10
102100037080 C4b-binding protein beta chain Human genes 0.000 claims description 10
102100021198 Chemerin-like receptor 2 Human genes 0.000 claims description 10
102100023416 G-protein coupled receptor 15 Human genes 0.000 claims description 10
102100033045 G-protein coupled receptor 4 Human genes 0.000 claims description 10
101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 claims description 10
101000798902 Homo sapiens Atypical chemokine receptor 4 Proteins 0.000 claims description 10
101000912618 Homo sapiens C-type lectin domain family 2 member B Proteins 0.000 claims description 10
101000740685 Homo sapiens C4b-binding protein alpha chain Proteins 0.000 claims description 10
101000740689 Homo sapiens C4b-binding protein beta chain Proteins 0.000 claims description 10
101000750094 Homo sapiens Chemerin-like receptor 2 Proteins 0.000 claims description 10
101000829794 Homo sapiens G-protein coupled receptor 15 Proteins 0.000 claims description 10
101000871138 Homo sapiens G-protein coupled receptor 4 Proteins 0.000 claims description 10
101000994815 Homo sapiens Interleukin-1 receptor accessory protein-like 1 Proteins 0.000 claims description 10
101001019591 Homo sapiens Interleukin-18-binding protein Proteins 0.000 claims description 10
101000975003 Homo sapiens Kallistatin Proteins 0.000 claims description 10
101000979578 Homo sapiens NK-tumor recognition protein Proteins 0.000 claims description 10
101000602167 Homo sapiens Neuroserpin Proteins 0.000 claims description 10
101001009517 Homo sapiens Probable G-protein coupled receptor 32 Proteins 0.000 claims description 10
101001009552 Homo sapiens Probable G-protein coupled receptor 34 Proteins 0.000 claims description 10
101000632467 Homo sapiens Pulmonary surfactant-associated protein D Proteins 0.000 claims description 10
101000650822 Homo sapiens Semaphorin-4B Proteins 0.000 claims description 10
102100034413 Interleukin-1 receptor accessory protein-like 1 Human genes 0.000 claims description 10
102100035017 Interleukin-18-binding protein Human genes 0.000 claims description 10
102100023012 Kallistatin Human genes 0.000 claims description 10
102100023384 NK-tumor recognition protein Human genes 0.000 claims description 10
102100037591 Neuroserpin Human genes 0.000 claims description 10
102100030321 Probable G-protein coupled receptor 32 Human genes 0.000 claims description 10
102100030263 Probable G-protein coupled receptor 34 Human genes 0.000 claims description 10
102100027845 Pulmonary surfactant-associated protein D Human genes 0.000 claims description 10
102100027717 Semaphorin-4B Human genes 0.000 claims description 10
239000003053 toxin Substances 0.000 claims description 10
231100000765 toxin Toxicity 0.000 claims description 10
108700012359 toxins Proteins 0.000 claims description 10
108010005173 SERPIN-B5 Proteins 0.000 claims description 9
102100030333 Serpin B5 Human genes 0.000 claims description 9
206010005003 Bladder cancer Diseases 0.000 claims description 8
208000008839 Kidney Neoplasms Diseases 0.000 claims description 8
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 8
206010038389 Renal cancer Diseases 0.000 claims description 8
208000000453 Skin Neoplasms Diseases 0.000 claims description 8
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 8
201000005787 hematologic cancer Diseases 0.000 claims description 8
208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 8
201000010982 kidney cancer Diseases 0.000 claims description 8
201000007270 liver cancer Diseases 0.000 claims description 8
208000014018 liver neoplasm Diseases 0.000 claims description 8
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 8
201000002528 pancreatic cancer Diseases 0.000 claims description 8
208000008443 pancreatic carcinoma Diseases 0.000 claims description 8
201000000849 skin cancer Diseases 0.000 claims description 8
201000005112 urinary bladder cancer Diseases 0.000 claims description 8
230000003308 immunostimulating effect Effects 0.000 claims description 7
238000009007 Diagnostic Kit Methods 0.000 claims description 6
229960001438 immunostimulant agent Drugs 0.000 claims description 6
239000003022 immunostimulating agent Substances 0.000 claims description 6
108010066676 Abrin Proteins 0.000 claims description 3
102000009016 Cholera Toxin Human genes 0.000 claims description 3
108010049048 Cholera Toxin Proteins 0.000 claims description 3
108010053187 Diphtheria Toxin Proteins 0.000 claims description 3
102000016607 Diphtheria Toxin Human genes 0.000 claims description 3
108700004714 Gelonium multiflorum GEL Proteins 0.000 claims description 3
101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 claims description 3
108010039491 Ricin Proteins 0.000 claims description 3
108010079723 Shiga Toxin Proteins 0.000 claims description 3
238000010253 intravenous injection Methods 0.000 claims description 2
108700028325 pokeweed antiviral Proteins 0.000 claims description 2
102000008847 Serpin Human genes 0.000 claims 1
108050000761 Serpin Proteins 0.000 claims 1
239000003001 serine protease inhibitor Substances 0.000 claims 1
210000000612 antigen-presenting cell Anatomy 0.000 abstract description 11
201000010099 disease Diseases 0.000 abstract description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
230000002265 prevention Effects 0.000 abstract description 2
210000004027 cell Anatomy 0.000 description 188
108090000623 proteins and genes Proteins 0.000 description 181
102000004169 proteins and genes Human genes 0.000 description 134
235000018102 proteins Nutrition 0.000 description 128
230000014509 gene expression Effects 0.000 description 77
238000003556 assay Methods 0.000 description 72
210000001744 T-lymphocyte Anatomy 0.000 description 62
108020004414 DNA Proteins 0.000 description 47
239000011230 binding agent Substances 0.000 description 43
239000002773 nucleotide Substances 0.000 description 42
125000003729 nucleotide group Chemical group 0.000 description 42
235000001014 amino acid Nutrition 0.000 description 41
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 41
108091032973 (ribonucleotides)n+m Proteins 0.000 description 39
229940024606 amino acid Drugs 0.000 description 37
150000001413 amino acids Chemical class 0.000 description 36
210000001519 tissue Anatomy 0.000 description 36
230000001965 increasing effect Effects 0.000 description 34
239000013615 primer Substances 0.000 description 33
239000013598 vector Substances 0.000 description 32
150000007523 nucleic acids Chemical class 0.000 description 31
230000002163 immunogen Effects 0.000 description 30
238000003364 immunohistochemistry Methods 0.000 description 30
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 28
239000003795 chemical substances by application Substances 0.000 description 28
239000002245 particle Substances 0.000 description 28
102000039446 nucleic acids Human genes 0.000 description 27
108020004707 nucleic acids Proteins 0.000 description 27
108091093037 Peptide nucleic acid Proteins 0.000 description 26
108091008874 T cell receptors Proteins 0.000 description 26
239000002671 adjuvant Substances 0.000 description 25
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 24
230000015572 biosynthetic process Effects 0.000 description 24
102100024952 Protein CBFA2T1 Human genes 0.000 description 23
238000009472 formulation Methods 0.000 description 23
238000009396 hybridization Methods 0.000 description 23
238000010186 staining Methods 0.000 description 23
239000003814 drug Substances 0.000 description 22
125000005647 linker group Chemical group 0.000 description 22
108091028043 Nucleic acid sequence Proteins 0.000 description 21
230000000694 effects Effects 0.000 description 21
239000013604 expression vector Substances 0.000 description 20
206010025323 Lymphomas Diseases 0.000 description 19
-1 antibodies Proteins 0.000 description 19
239000002299 complementary DNA Substances 0.000 description 19
150000001875 compounds Chemical class 0.000 description 19
230000004927 fusion Effects 0.000 description 19
230000003321 amplification Effects 0.000 description 18
238000003199 nucleic acid amplification method Methods 0.000 description 18
238000003752 polymerase chain reaction Methods 0.000 description 18
108091092562 ribozyme Proteins 0.000 description 18
108090000994 Catalytic RNA Proteins 0.000 description 17
102000053642 Catalytic RNA Human genes 0.000 description 17
108020004999 messenger RNA Proteins 0.000 description 17
150000003839 salts Chemical class 0.000 description 17
239000007787 solid Substances 0.000 description 17
238000003786 synthesis reaction Methods 0.000 description 17
210000004881 tumor cell Anatomy 0.000 description 17
238000007792 addition Methods 0.000 description 16
230000014616 translation Effects 0.000 description 16
230000028993 immune response Effects 0.000 description 15
125000006853 reporter group Chemical group 0.000 description 15
239000000243 solution Substances 0.000 description 15
230000001225 therapeutic effect Effects 0.000 description 15
229960005486 vaccine Drugs 0.000 description 15
238000004458 analytical method Methods 0.000 description 14
239000002585 base Substances 0.000 description 14
239000012528 membrane Substances 0.000 description 14
210000004379 membrane Anatomy 0.000 description 14
239000000126 substance Substances 0.000 description 14
238000013519 translation Methods 0.000 description 14
238000012384 transportation and delivery Methods 0.000 description 14
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 13
238000013459 approach Methods 0.000 description 13
210000003719 b-lymphocyte Anatomy 0.000 description 13
230000006037 cell lysis Effects 0.000 description 13
238000012217 deletion Methods 0.000 description 13
230000037430 deletion Effects 0.000 description 13
238000004519 manufacturing process Methods 0.000 description 13
230000004048 modification Effects 0.000 description 13
238000012986 modification Methods 0.000 description 13
238000006467 substitution reaction Methods 0.000 description 13
230000004913 activation Effects 0.000 description 12
239000002502 liposome Substances 0.000 description 12
239000002987 primer (paints) Substances 0.000 description 12
230000008569 process Effects 0.000 description 12
238000000746 purification Methods 0.000 description 12
239000002904 solvent Substances 0.000 description 12
102000053602 DNA Human genes 0.000 description 11
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
108060003951 Immunoglobulin Proteins 0.000 description 11
102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 11
102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 11
241000700605 Viruses Species 0.000 description 11
230000000692 anti-sense effect Effects 0.000 description 11
210000004369 blood Anatomy 0.000 description 11
239000008280 blood Substances 0.000 description 11
230000009089 cytolysis Effects 0.000 description 11
102000018358 immunoglobulin Human genes 0.000 description 11
230000003993 interaction Effects 0.000 description 11
239000000758 substrate Substances 0.000 description 11
102000004127 Cytokines Human genes 0.000 description 10
108090000695 Cytokines Proteins 0.000 description 10
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 10
241001465754 Metazoa Species 0.000 description 10
210000000481 breast Anatomy 0.000 description 10
238000003776 cleavage reaction Methods 0.000 description 10
238000010790 dilution Methods 0.000 description 10
239000012895 dilution Substances 0.000 description 10
239000000047 product Substances 0.000 description 10
230000004044 response Effects 0.000 description 10
230000007017 scission Effects 0.000 description 10
238000012360 testing method Methods 0.000 description 10
108091026890 Coding region Proteins 0.000 description 9
230000006052 T cell proliferation Effects 0.000 description 9
BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 9
229940079593 drug Drugs 0.000 description 9
230000002255 enzymatic effect Effects 0.000 description 9
230000001900 immune effect Effects 0.000 description 9
238000000338 in vitro Methods 0.000 description 9
239000000463 material Substances 0.000 description 9
238000002360 preparation method Methods 0.000 description 9
238000010561 standard procedure Methods 0.000 description 9
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 8
238000002965 ELISA Methods 0.000 description 8
125000000539 amino acid group Chemical group 0.000 description 8
239000000074 antisense oligonucleotide Substances 0.000 description 8
238000012230 antisense oligonucleotides Methods 0.000 description 8
239000011324 bead Substances 0.000 description 8
239000000872 buffer Substances 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
230000000875 corresponding effect Effects 0.000 description 8
230000007423 decrease Effects 0.000 description 8
238000005516 engineering process Methods 0.000 description 8
230000001976 improved effect Effects 0.000 description 8
238000011534 incubation Methods 0.000 description 8
239000003550 marker Substances 0.000 description 8
238000003753 real-time PCR Methods 0.000 description 8
241000894007 species Species 0.000 description 8
238000013518 transcription Methods 0.000 description 8
230000035897 transcription Effects 0.000 description 8
241000699666 Mus <mouse, genus> Species 0.000 description 7
230000002776 aggregation Effects 0.000 description 7
230000001580 bacterial effect Effects 0.000 description 7
238000010367 cloning Methods 0.000 description 7
210000000981 epithelium Anatomy 0.000 description 7
238000009169 immunotherapy Methods 0.000 description 7
238000001727 in vivo Methods 0.000 description 7
239000007788 liquid Substances 0.000 description 7
210000004698 lymphocyte Anatomy 0.000 description 7
230000007246 mechanism Effects 0.000 description 7
239000012071 phase Substances 0.000 description 7
229920000056 polyoxyethylene ether Polymers 0.000 description 7
239000011148 porous material Substances 0.000 description 7
230000009257 reactivity Effects 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
210000002966 serum Anatomy 0.000 description 7
230000035882 stress Effects 0.000 description 7
239000006228 supernatant Substances 0.000 description 7
108020004705 Codon Proteins 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
229920001917 Ficoll Polymers 0.000 description 6
230000005526 G1 to G0 transition Effects 0.000 description 6
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 6
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
206010060862 Prostate cancer Diseases 0.000 description 6
241000283984 Rodentia Species 0.000 description 6
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 6
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 6
239000002253 acid Substances 0.000 description 6
238000004220 aggregation Methods 0.000 description 6
210000004204 blood vessel Anatomy 0.000 description 6
239000000969 carrier Substances 0.000 description 6
238000012512 characterization method Methods 0.000 description 6
210000001072 colon Anatomy 0.000 description 6
230000001419 dependent effect Effects 0.000 description 6
239000003623 enhancer Substances 0.000 description 6
229940088598 enzyme Drugs 0.000 description 6
230000006870 function Effects 0.000 description 6
238000001415 gene therapy Methods 0.000 description 6
230000001939 inductive effect Effects 0.000 description 6
230000003834 intracellular effect Effects 0.000 description 6
206010073095 invasive ductal breast carcinoma Diseases 0.000 description 6
201000010985 invasive ductal carcinoma Diseases 0.000 description 6
239000013612 plasmid Substances 0.000 description 6
229920001282 polysaccharide Polymers 0.000 description 6
239000005017 polysaccharide Substances 0.000 description 6
239000000843 powder Substances 0.000 description 6
230000035755 proliferation Effects 0.000 description 6
210000002307 prostate Anatomy 0.000 description 6
238000011160 research Methods 0.000 description 6
230000002441 reversible effect Effects 0.000 description 6
229930182490 saponin Natural products 0.000 description 6
235000017709 saponins Nutrition 0.000 description 6
150000007949 saponins Chemical class 0.000 description 6
230000035945 sensitivity Effects 0.000 description 6
239000007790 solid phase Substances 0.000 description 6
229940124597 therapeutic agent Drugs 0.000 description 6
239000003981 vehicle Substances 0.000 description 6
102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 5
108010085238 Actins Proteins 0.000 description 5
241000894006 Bacteria Species 0.000 description 5
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
239000004471 Glycine Substances 0.000 description 5
241000282412 Homo Species 0.000 description 5
108091092195 Intron Proteins 0.000 description 5
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
239000004472 Lysine Substances 0.000 description 5
208000000236 Prostatic Neoplasms Diseases 0.000 description 5
108020004511 Recombinant DNA Proteins 0.000 description 5
108091081024 Start codon Proteins 0.000 description 5
241000700618 Vaccinia virus Species 0.000 description 5
206010046865 Vaccinia virus infection Diseases 0.000 description 5
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
125000000217 alkyl group Chemical group 0.000 description 5
230000008878 coupling Effects 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
230000001186 cumulative effect Effects 0.000 description 5
238000013461 design Methods 0.000 description 5
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 5
238000010494 dissociation reaction Methods 0.000 description 5
230000005593 dissociations Effects 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
238000000684 flow cytometry Methods 0.000 description 5
230000013595 glycosylation Effects 0.000 description 5
238000006206 glycosylation reaction Methods 0.000 description 5
238000003018 immunoassay Methods 0.000 description 5
230000005847 immunogenicity Effects 0.000 description 5
238000007918 intramuscular administration Methods 0.000 description 5
238000001990 intravenous administration Methods 0.000 description 5
230000000670 limiting effect Effects 0.000 description 5
229920006008 lipopolysaccharide Polymers 0.000 description 5
230000003211 malignant effect Effects 0.000 description 5
239000011159 matrix material Substances 0.000 description 5
238000010369 molecular cloning Methods 0.000 description 5
230000035772 mutation Effects 0.000 description 5
239000002751 oligonucleotide probe Substances 0.000 description 5
230000002018 overexpression Effects 0.000 description 5
238000010647 peptide synthesis reaction Methods 0.000 description 5
239000002953 phosphate buffered saline Substances 0.000 description 5
229920000642 polymer Polymers 0.000 description 5
150000004804 polysaccharides Chemical class 0.000 description 5
230000001105 regulatory effect Effects 0.000 description 5
238000007423 screening assay Methods 0.000 description 5
238000002741 site-directed mutagenesis Methods 0.000 description 5
238000007920 subcutaneous administration Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
241000701161 unidentified adenovirus Species 0.000 description 5
208000007089 vaccinia Diseases 0.000 description 5
230000003612 virological effect Effects 0.000 description 5
239000004475 Arginine Substances 0.000 description 4
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
239000003155 DNA primer Substances 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
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 4
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
239000004473 Threonine Substances 0.000 description 4
108020004440 Thymidine kinase Proteins 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000009471 action Effects 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
230000000259 anti-tumor effect Effects 0.000 description 4
230000000890 antigenic effect Effects 0.000 description 4
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
235000009582 asparagine Nutrition 0.000 description 4
229960001230 asparagine Drugs 0.000 description 4
235000003704 aspartic acid Nutrition 0.000 description 4
230000008901 benefit Effects 0.000 description 4
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
239000002775 capsule Substances 0.000 description 4
230000010261 cell growth Effects 0.000 description 4
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
239000011248 coating agent Substances 0.000 description 4
238000000576 coating method Methods 0.000 description 4
208000029742 colonic neoplasm Diseases 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
229940000406 drug candidate Drugs 0.000 description 4
239000012636 effector Substances 0.000 description 4
235000013922 glutamic acid Nutrition 0.000 description 4
239000004220 glutamic acid Substances 0.000 description 4
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
229940127121 immunoconjugate Drugs 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000003780 insertion Methods 0.000 description 4
230000037431 insertion Effects 0.000 description 4
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
229960000310 isoleucine Drugs 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
210000004962 mammalian cell Anatomy 0.000 description 4
239000004005 microsphere Substances 0.000 description 4
201000010225 mixed cell type cancer Diseases 0.000 description 4
208000029638 mixed neoplasm Diseases 0.000 description 4
229940035032 monophosphoryl lipid a Drugs 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
230000036961 partial effect Effects 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
238000012545 processing Methods 0.000 description 4
RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
230000006798 recombination Effects 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
230000010076 replication Effects 0.000 description 4
238000003757 reverse transcription PCR Methods 0.000 description 4
238000012216 screening Methods 0.000 description 4
238000000926 separation method Methods 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
239000003826 tablet Substances 0.000 description 4
239000004474 valine Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
108700028369 Alleles Proteins 0.000 description 3
102100030988 Angiotensin-converting enzyme Human genes 0.000 description 3
108020000948 Antisense Oligonucleotides Proteins 0.000 description 3
241000700663 Avipoxvirus Species 0.000 description 3
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
206010009944 Colon cancer Diseases 0.000 description 3
102100029727 Enteropeptidase Human genes 0.000 description 3
108010013369 Enteropeptidase Proteins 0.000 description 3
101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 3
108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
102100022338 Integrin alpha-M Human genes 0.000 description 3
108010002350 Interleukin-2 Proteins 0.000 description 3
102000000588 Interleukin-2 Human genes 0.000 description 3
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
206010035226 Plasma cell myeloma Diseases 0.000 description 3
239000004698 Polyethylene Substances 0.000 description 3
108091030071 RNAI Proteins 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
102000006601 Thymidine Kinase Human genes 0.000 description 3
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 3
238000009825 accumulation Methods 0.000 description 3
230000002411 adverse Effects 0.000 description 3
238000001042 affinity chromatography Methods 0.000 description 3
238000013019 agitation Methods 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
229960000074 biopharmaceutical Drugs 0.000 description 3
238000001574 biopsy Methods 0.000 description 3
210000001185 bone marrow Anatomy 0.000 description 3
DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 3
230000015556 catabolic process Effects 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
230000032823 cell division Effects 0.000 description 3
238000001516 cell proliferation assay Methods 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
238000003501 co-culture Methods 0.000 description 3
230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
238000013270 controlled release Methods 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
GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
210000004443 dendritic cell Anatomy 0.000 description 3
238000002405 diagnostic procedure Methods 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000000975 dye Substances 0.000 description 3
210000003743 erythrocyte Anatomy 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
108020001507 fusion proteins Proteins 0.000 description 3
102000037865 fusion proteins Human genes 0.000 description 3
239000007789 gas Substances 0.000 description 3
238000005227 gel permeation chromatography Methods 0.000 description 3
238000001476 gene delivery Methods 0.000 description 3
230000009368 gene silencing by RNA Effects 0.000 description 3
230000002068 genetic effect Effects 0.000 description 3
230000012010 growth Effects 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
210000004408 hybridoma Anatomy 0.000 description 3
210000000987 immune system Anatomy 0.000 description 3
230000036039 immunity Effects 0.000 description 3
208000015181 infectious disease Diseases 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
230000002452 interceptive effect Effects 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
238000002372 labelling Methods 0.000 description 3
150000002632 lipids Chemical class 0.000 description 3
239000006166 lysate Substances 0.000 description 3
210000002540 macrophage Anatomy 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
206010061289 metastatic neoplasm Diseases 0.000 description 3
239000011859 microparticle Substances 0.000 description 3
238000012544 monitoring process Methods 0.000 description 3
238000002703 mutagenesis Methods 0.000 description 3
231100000350 mutagenesis Toxicity 0.000 description 3
201000000050 myeloid neoplasm Diseases 0.000 description 3
239000002088 nanocapsule Substances 0.000 description 3
210000000822 natural killer cell Anatomy 0.000 description 3
239000013642 negative control Substances 0.000 description 3
239000007764 o/w emulsion Substances 0.000 description 3
229960002378 oftasceine Drugs 0.000 description 3
210000005259 peripheral blood Anatomy 0.000 description 3
239000011886 peripheral blood Substances 0.000 description 3
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
229940051841 polyoxyethylene ether Drugs 0.000 description 3
238000000159 protein binding assay Methods 0.000 description 3
150000003212 purines Chemical class 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
230000008707 rearrangement Effects 0.000 description 3
238000010188 recombinant method Methods 0.000 description 3
230000001177 retroviral effect Effects 0.000 description 3
238000012163 sequencing technique Methods 0.000 description 3
238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 3
150000003384 small molecules Chemical class 0.000 description 3
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
238000001179 sorption measurement Methods 0.000 description 3
210000004989 spleen cell Anatomy 0.000 description 3
229940104230 thymidine Drugs 0.000 description 3
239000011732 tocopherol Substances 0.000 description 3
229960001295 tocopherol Drugs 0.000 description 3
229930003799 tocopherol Natural products 0.000 description 3
235000010384 tocopherol Nutrition 0.000 description 3
230000002103 transcriptional effect Effects 0.000 description 3
238000011269 treatment regimen Methods 0.000 description 3
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
238000005406 washing Methods 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
238000001262 western blot Methods 0.000 description 3
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 2
241001227713 Chiron Species 0.000 description 2
241000759568 Corixa Species 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
102100025137 Early activation antigen CD69 Human genes 0.000 description 2
241000196324 Embryophyta Species 0.000 description 2
206010014611 Encephalitis venezuelan equine Diseases 0.000 description 2
108090000371 Esterases Proteins 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
241000724709 Hepatitis delta virus Species 0.000 description 2
101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 2
101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
101000582320 Homo sapiens Neurogenic differentiation factor 6 Proteins 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 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
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
241000239218 Limulus Species 0.000 description 2
108700041567 MDR Genes Proteins 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
102100030589 Neurogenic differentiation factor 6 Human genes 0.000 description 2
239000000020 Nitrocellulose Substances 0.000 description 2
108091005461 Nucleic proteins Proteins 0.000 description 2
108020005187 Oligonucleotide Probes Proteins 0.000 description 2
238000012408 PCR amplification Methods 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
108010047620 Phytohemagglutinins Proteins 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
239000004793 Polystyrene Substances 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
230000007022 RNA scission Effects 0.000 description 2
238000011529 RT qPCR Methods 0.000 description 2
238000010240 RT-PCR analysis Methods 0.000 description 2
102000004167 Ribonuclease P Human genes 0.000 description 2
108090000621 Ribonuclease P Proteins 0.000 description 2
241000220317 Rosa Species 0.000 description 2
241000714474 Rous sarcoma virus Species 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
108091027967 Small hairpin RNA Proteins 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
241000723873 Tobacco mosaic virus Species 0.000 description 2
102000040945 Transcription factor Human genes 0.000 description 2
108091023040 Transcription factor Proteins 0.000 description 2
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
108091023045 Untranslated Region Proteins 0.000 description 2
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
208000002687 Venezuelan Equine Encephalomyelitis Diseases 0.000 description 2
201000009145 Venezuelan equine encephalitis Diseases 0.000 description 2
FHICGHSMIPIAPL-HDYAAECPSA-N [2-[3-[6-[3-[(5R,6aS,6bR,12aR)-10-[6-[2-[2-[4,5-dihydroxy-3-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]ethoxy]ethyl]-3,4,5-trihydroxyoxan-2-yl]oxy-5-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carbonyl]peroxypropyl]-5-[[5-[8-[3,5-dihydroxy-4-(3,4,5-trihydroxyoxan-2-yl)oxyoxan-2-yl]octoxy]-3,4-dihydroxy-6-methyloxan-2-yl]methoxy]-3,4-dihydroxyoxan-2-yl]propoxymethyl]-5-hydroxy-3-[(6S)-6-hydroxy-2,6-dimethylocta-2,7-dienoyl]oxy-6-methyloxan-4-yl] (2E,6S)-6-hydroxy-2-(hydroxymethyl)-6-methylocta-2,7-dienoate Chemical compound C=C[C@@](C)(O)CCC=C(C)C(=O)OC1C(OC(=O)C(\CO)=C\CC[C@](C)(O)C=C)C(O)C(C)OC1COCCCC1C(O)C(O)C(OCC2C(C(O)C(OCCCCCCCCC3C(C(OC4C(C(O)C(O)CO4)O)C(O)CO3)O)C(C)O2)O)C(CCCOOC(=O)C23C(CC(C)(C)CC2)C=2[C@@]([C@]4(C)CCC5C(C)(C)C(OC6C(C(O)C(O)C(CCOCCC7C(C(O)C(O)CO7)OC7C(C(O)C(O)CO7)O)O6)O)CC[C@]5(C)C4CC=2)(C)C[C@H]3O)O1 FHICGHSMIPIAPL-HDYAAECPSA-N 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
230000021736 acetylation Effects 0.000 description 2
238000006640 acetylation reaction Methods 0.000 description 2
239000013543 active substance Substances 0.000 description 2
208000009956 adenocarcinoma Diseases 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
229940024545 aluminum hydroxide Drugs 0.000 description 2
150000001412 amines Chemical group 0.000 description 2
230000003302 anti-idiotype Effects 0.000 description 2
239000002246 antineoplastic agent Substances 0.000 description 2
239000012736 aqueous medium Substances 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
230000001588 bifunctional effect Effects 0.000 description 2
239000013060 biological fluid Substances 0.000 description 2
230000036760 body temperature Effects 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
238000011088 calibration curve Methods 0.000 description 2
150000001720 carbohydrates Chemical group 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
229940044683 chemotherapy drug Drugs 0.000 description 2
235000012000 cholesterol Nutrition 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
201000010897 colon adenocarcinoma Diseases 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
238000012875 competitive assay Methods 0.000 description 2
238000010668 complexation reaction Methods 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
238000012258 culturing Methods 0.000 description 2
210000000805 cytoplasm Anatomy 0.000 description 2
210000000172 cytosol Anatomy 0.000 description 2
210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
230000001472 cytotoxic effect Effects 0.000 description 2
231100000135 cytotoxicity Toxicity 0.000 description 2
230000003013 cytotoxicity Effects 0.000 description 2
230000007123 defense Effects 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
230000004069 differentiation Effects 0.000 description 2
UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 2
UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 2
239000000539 dimer Substances 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
230000007717 exclusion Effects 0.000 description 2
238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
239000007850 fluorescent dye Substances 0.000 description 2
238000001502 gel electrophoresis Methods 0.000 description 2
239000011521 glass Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
238000002744 homologous recombination Methods 0.000 description 2
230000006801 homologous recombination Effects 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
238000002169 hydrotherapy Methods 0.000 description 2
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
238000007901 in situ hybridization Methods 0.000 description 2
239000000411 inducer Substances 0.000 description 2
230000006698 induction Effects 0.000 description 2
230000036512 infertility Effects 0.000 description 2
238000001802 infusion Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
230000002147 killing effect Effects 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000004816 latex Substances 0.000 description 2
229920000126 latex Polymers 0.000 description 2
230000033001 locomotion Effects 0.000 description 2
208000037841 lung tumor Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000006249 magnetic particle Substances 0.000 description 2
238000012423 maintenance Methods 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
229960000485 methotrexate Drugs 0.000 description 2
244000005700 microbiome Species 0.000 description 2
229960004857 mitomycin Drugs 0.000 description 2
238000007799 mixed lymphocyte reaction assay Methods 0.000 description 2
210000001616 monocyte Anatomy 0.000 description 2
229920001220 nitrocellulos Polymers 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
238000010606 normalization Methods 0.000 description 2
238000007899 nucleic acid hybridization Methods 0.000 description 2
108091008819 oncoproteins Proteins 0.000 description 2
102000027450 oncoproteins Human genes 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
210000000496 pancreas Anatomy 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
230000037361 pathway Effects 0.000 description 2
150000003904 phospholipids Chemical class 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
230000001766 physiological effect Effects 0.000 description 2
230000001885 phytohemagglutinin Effects 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000004033 plastic Substances 0.000 description 2
229920003023 plastic Polymers 0.000 description 2
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
229920002223 polystyrene Polymers 0.000 description 2
239000004800 polyvinyl chloride Substances 0.000 description 2
229920000915 polyvinyl chloride Polymers 0.000 description 2
230000001323 posttranslational effect Effects 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000000069 prophylactic effect Effects 0.000 description 2
238000001243 protein synthesis Methods 0.000 description 2
229950010131 puromycin Drugs 0.000 description 2
239000001397 quillaja saponaria molina bark Substances 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
238000003127 radioimmunoassay Methods 0.000 description 2
238000005215 recombination Methods 0.000 description 2
230000004043 responsiveness Effects 0.000 description 2
230000000717 retained effect Effects 0.000 description 2
238000010839 reverse transcription Methods 0.000 description 2
238000012552 review Methods 0.000 description 2
238000001115 scanning electrochemical microscopy Methods 0.000 description 2
230000003248 secreting effect Effects 0.000 description 2
239000006152 selective media Substances 0.000 description 2
238000004513 sizing Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000010532 solid phase synthesis reaction Methods 0.000 description 2
230000002269 spontaneous effect Effects 0.000 description 2
206010041823 squamous cell carcinoma Diseases 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
125000003396 thiol group Chemical group [H]S* 0.000 description 2
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
230000009258 tissue cross reactivity Effects 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
238000001890 transfection Methods 0.000 description 2
230000032258 transport Effects 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical group [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
229910052722 tritium Inorganic materials 0.000 description 2
241001515965 unidentified phage Species 0.000 description 2
241001430294 unidentified retrovirus Species 0.000 description 2
238000011144 upstream manufacturing Methods 0.000 description 2
239000013603 viral vector Substances 0.000 description 2
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical compound NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 1
TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 1
239000013607 AAV vector Substances 0.000 description 1
102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
101150094949 APRT gene Proteins 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
229930024421 Adenine Natural products 0.000 description 1
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
241000710929 Alphavirus Species 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
241000024188 Andala Species 0.000 description 1
102000006306 Antigen Receptors Human genes 0.000 description 1
241000272478 Aquila Species 0.000 description 1
206010003445 Ascites Diseases 0.000 description 1
102100032306 Aurora kinase B Human genes 0.000 description 1
108090000749 Aurora kinase B Proteins 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
208000003950 B-cell lymphoma Diseases 0.000 description 1
102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
QOFRNSMLZCPQKL-KTIIIUPTSA-N CCN(CC)CC.CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)NCCO[C@@H]1O[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@H]1NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC Chemical compound CCN(CC)CC.CCCCCCCCCCCCCC(=O)O[C@H](CCCCCCCCCCC)CC(=O)NCCO[C@@H]1O[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@H]1NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC QOFRNSMLZCPQKL-KTIIIUPTSA-N 0.000 description 1
102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
102000049320 CD36 Human genes 0.000 description 1
108010045374 CD36 Antigens Proteins 0.000 description 1
101150013553 CD40 gene Proteins 0.000 description 1
102100032937 CD40 ligand Human genes 0.000 description 1
102100032912 CD44 antigen Human genes 0.000 description 1
241000305761 Calidris canutus Species 0.000 description 1
241000178270 Canarypox virus Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
101710132601 Capsid protein Proteins 0.000 description 1
102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
108010078791 Carrier Proteins Proteins 0.000 description 1
241000701489 Cauliflower mosaic virus Species 0.000 description 1
241001529572 Chaceon affinis Species 0.000 description 1
229920001661 Chitosan Polymers 0.000 description 1
239000005496 Chlorsulfuron Substances 0.000 description 1
108010009685 Cholinergic Receptors Proteins 0.000 description 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
108700010070 Codon Usage Proteins 0.000 description 1
208000003322 Coinfection Diseases 0.000 description 1
108010069112 Complement System Proteins Proteins 0.000 description 1
102000000989 Complement System Proteins Human genes 0.000 description 1
108010047041 Complementarity Determining Regions Proteins 0.000 description 1
241000557626 Corvus corax Species 0.000 description 1
108050006400 Cyclin Proteins 0.000 description 1
102000016736 Cyclin Human genes 0.000 description 1
UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
YVGGHNCTFXOJCH-UHFFFAOYSA-N DDT Chemical compound C1=CC(Cl)=CC=C1C(C(Cl)(Cl)Cl)C1=CC=C(Cl)C=C1 YVGGHNCTFXOJCH-UHFFFAOYSA-N 0.000 description 1
101150074155 DHFR gene Proteins 0.000 description 1
230000006820 DNA synthesis Effects 0.000 description 1
238000007900 DNA-DNA hybridization Methods 0.000 description 1
108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
102000007260 Deoxyribonuclease I Human genes 0.000 description 1
108010008532 Deoxyribonuclease I Proteins 0.000 description 1
241000702421 Dependoparvovirus Species 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
108010024212 E-Selectin Proteins 0.000 description 1
102100023471 E-selectin Human genes 0.000 description 1
238000012286 ELISA Assay Methods 0.000 description 1
108010042407 Endonucleases Proteins 0.000 description 1
102000004533 Endonucleases Human genes 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
101000686777 Escherichia phage T7 T7 RNA polymerase Proteins 0.000 description 1
108010074860 Factor Xa Proteins 0.000 description 1
241000192125 Firmicutes Species 0.000 description 1
BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
241000700662 Fowlpox virus Species 0.000 description 1
240000007108 Fuchsia magellanica Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
102000053187 Glucuronidase Human genes 0.000 description 1
108010060309 Glucuronidase Proteins 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
102100035716 Glycophorin-A Human genes 0.000 description 1
108091005250 Glycophorins Proteins 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins 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
229920000084 Gum arabic Polymers 0.000 description 1
102000006354 HLA-DR Antigens Human genes 0.000 description 1
108010058597 HLA-DR Antigens Proteins 0.000 description 1
102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
108091027305 Heteroduplex Proteins 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 1
101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 1
101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 1
101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 1
101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 1
101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 1
101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
101000819111 Homo sapiens Trans-acting T-cell-specific transcription factor GATA-3 Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
108020005350 Initiator Codon Proteins 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
102100025306 Integrin alpha-IIb Human genes 0.000 description 1
102100022297 Integrin alpha-X Human genes 0.000 description 1
102100025304 Integrin beta-1 Human genes 0.000 description 1
108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
102100037850 Interferon gamma Human genes 0.000 description 1
108010074328 Interferon-gamma Proteins 0.000 description 1
108090000174 Interleukin-10 Proteins 0.000 description 1
108010065805 Interleukin-12 Proteins 0.000 description 1
102000013462 Interleukin-12 Human genes 0.000 description 1
108090000978 Interleukin-4 Proteins 0.000 description 1
108090001005 Interleukin-6 Proteins 0.000 description 1
108010002586 Interleukin-7 Proteins 0.000 description 1
102000000704 Interleukin-7 Human genes 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
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 1
125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
125000000773 L-serino group Chemical group [H]OC(=O)[C@@]([H])(N([H])*)C([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
108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
108090001090 Lectins Proteins 0.000 description 1
102000004856 Lectins Human genes 0.000 description 1
241000186779 Listeria monocytogenes Species 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
102000001691 Member 3 Group F Nuclear Receptor Subfamily 1 Human genes 0.000 description 1
108010029279 Member 3 Group F Nuclear Receptor Subfamily 1 Proteins 0.000 description 1
244000246386 Mentha pulegium Species 0.000 description 1
235000016257 Mentha pulegium Nutrition 0.000 description 1
235000004357 Mentha x piperita Nutrition 0.000 description 1
101100261636 Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg) trpB2 gene Proteins 0.000 description 1
102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
241000204795 Muraena helena Species 0.000 description 1
241001529936 Murinae Species 0.000 description 1
101000935589 Mus musculus Flavin reductase (NADPH) Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
241000238367 Mya arenaria Species 0.000 description 1
241000187479 Mycobacterium tuberculosis Species 0.000 description 1
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
108091061960 Naked DNA Proteins 0.000 description 1
229930193140 Neomycin Natural products 0.000 description 1
102000003729 Neprilysin Human genes 0.000 description 1
108090000028 Neprilysin Proteins 0.000 description 1
102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
238000000636 Northern blotting Methods 0.000 description 1
108020004711 Nucleic Acid Probes Proteins 0.000 description 1
102000011931 Nucleoproteins Human genes 0.000 description 1
108010061100 Nucleoproteins Proteins 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
108010038807 Oligopeptides Proteins 0.000 description 1
102000015636 Oligopeptides Human genes 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
101710160107 Outer membrane protein A Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
108090000526 Papain Proteins 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
108090000284 Pepsin A Proteins 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
201000005702 Pertussis Diseases 0.000 description 1
244000046052 Phaseolus vulgaris Species 0.000 description 1
235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
101100124346 Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01) hisCD gene Proteins 0.000 description 1
102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
241000276498 Pollachius virens Species 0.000 description 1
206010036790 Productive cough Diseases 0.000 description 1
239000004365 Protease Substances 0.000 description 1
108010076504 Protein Sorting Signals Proteins 0.000 description 1
229940123573 Protein synthesis inhibitor Drugs 0.000 description 1
206010037660 Pyrexia Diseases 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
108010066717 Q beta Replicase Proteins 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
108020004518 RNA Probes Proteins 0.000 description 1
239000003391 RNA probe Substances 0.000 description 1
241000700159 Rattus Species 0.000 description 1
102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
102100038081 Signal transducer CD24 Human genes 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
108020004682 Single-Stranded DNA Proteins 0.000 description 1
108020004459 Small interfering RNA Proteins 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
238000002105 Southern blotting Methods 0.000 description 1
241000251131 Sphyrna Species 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
230000024932 T cell mediated immunity Effects 0.000 description 1
230000005867 T cell response Effects 0.000 description 1
102100025237 T-cell surface antigen CD2 Human genes 0.000 description 1
102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 1
102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
108010006785 Taq Polymerase Proteins 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
210000000447 Th1 cell Anatomy 0.000 description 1
210000000068 Th17 cell Anatomy 0.000 description 1
210000004241 Th2 cell Anatomy 0.000 description 1
241000906446 Theraps Species 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
102100036407 Thioredoxin Human genes 0.000 description 1
101710120037 Toxin CcdB Proteins 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102100021386 Trans-acting T-cell-specific transcription factor GATA-3 Human genes 0.000 description 1
102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
101150117115 V gene Proteins 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
102100035071 Vimentin Human genes 0.000 description 1
108010065472 Vimentin Proteins 0.000 description 1
239000003070 absorption delaying agent Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
230000001133 acceleration Effects 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
102000034337 acetylcholine receptors Human genes 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000000654 additive Substances 0.000 description 1
229960000643 adenine Drugs 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
238000001261 affinity purification Methods 0.000 description 1
238000005054 agglomeration Methods 0.000 description 1
125000003172 aldehyde group Chemical group 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000000735 allogeneic effect Effects 0.000 description 1
239000012637 allosteric effector Substances 0.000 description 1
230000004075 alteration Effects 0.000 description 1
229940037003 alum Drugs 0.000 description 1
ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
229940024546 aluminum hydroxide gel Drugs 0.000 description 1
SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
229940126575 aminoglycoside Drugs 0.000 description 1
229960003896 aminopterin Drugs 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000012801 analytical assay Methods 0.000 description 1
238000013103 analytical ultracentrifugation Methods 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
235000010208 anthocyanin Nutrition 0.000 description 1
229930002877 anthocyanin Natural products 0.000 description 1
239000004410 anthocyanin Substances 0.000 description 1
150000004636 anthocyanins Chemical class 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000000840 anti-viral effect Effects 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
230000005975 antitumor immune response Effects 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
238000002820 assay format Methods 0.000 description 1
239000000305 astragalus gummifer gum Substances 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
230000003190 augmentative effect Effects 0.000 description 1
230000006472 autoimmune response Effects 0.000 description 1
239000000022 bacteriostatic agent Substances 0.000 description 1
230000037429 base substitution Effects 0.000 description 1
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
238000002306 biochemical method Methods 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
229920000249 biocompatible polymer Polymers 0.000 description 1
230000008827 biological function Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
239000002981 blocking agent Substances 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
201000008275 breast carcinoma Diseases 0.000 description 1
229950004398 broxuridine Drugs 0.000 description 1
239000006189 buccal tablet Substances 0.000 description 1
239000007975 buffered saline Substances 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
229940087373 calcium oxide Drugs 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
238000002619 cancer immunotherapy Methods 0.000 description 1
238000001818 capillary gel electrophoresis Methods 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000021523 carboxylation Effects 0.000 description 1
238000006473 carboxylation reaction Methods 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
108020001778 catalytic domains Proteins 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
238000000423 cell based assay Methods 0.000 description 1
238000012832 cell culture technique Methods 0.000 description 1
230000022131 cell cycle Effects 0.000 description 1
230000011712 cell development Effects 0.000 description 1
230000007910 cell fusion Effects 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000007969 cellular immunity Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
239000007958 cherry flavor Substances 0.000 description 1
VJYIFXVZLXQVHO-UHFFFAOYSA-N chlorsulfuron Chemical compound COC1=NC(C)=NC(NC(=O)NS(=O)(=O)C=2C(=CC=CC=2)Cl)=N1 VJYIFXVZLXQVHO-UHFFFAOYSA-N 0.000 description 1
229910052804 chromium Inorganic materials 0.000 description 1
239000011651 chromium Substances 0.000 description 1
230000002759 chromosomal effect Effects 0.000 description 1
238000002983 circular dichroism Methods 0.000 description 1
230000035602 clotting Effects 0.000 description 1
230000004186 co-expression Effects 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
239000000084 colloidal system Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
239000007771 core particle Substances 0.000 description 1
238000012937 correction Methods 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
239000003431 cross linking reagent Substances 0.000 description 1
238000012926 crystallographic analysis Methods 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
238000011461 current therapy Methods 0.000 description 1
229960003067 cystine Drugs 0.000 description 1
UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
238000002784 cytotoxicity assay Methods 0.000 description 1
231100000263 cytotoxicity test Toxicity 0.000 description 1
230000006378 damage Effects 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000000432 density-gradient centrifugation Methods 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000000378 dietary effect Effects 0.000 description 1
238000000113 differential scanning calorimetry Methods 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000002612 dispersion medium Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229960004887 ferric hydroxide Drugs 0.000 description 1
239000000835 fiber Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000001506 fluorescence spectroscopy Methods 0.000 description 1
108091006047 fluorescent proteins Proteins 0.000 description 1
102000034287 fluorescent proteins Human genes 0.000 description 1
238000011010 flushing procedure Methods 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
238000010359 gene isolation Methods 0.000 description 1
102000054766 genetic haplotypes Human genes 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
230000036541 health Effects 0.000 description 1
230000005802 health problem Effects 0.000 description 1
230000008642 heat stress Effects 0.000 description 1
239000001307 helium Substances 0.000 description 1
229910052734 helium Inorganic materials 0.000 description 1
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
210000002443 helper t lymphocyte Anatomy 0.000 description 1
208000002672 hepatitis B Diseases 0.000 description 1
210000003494 hepatocyte Anatomy 0.000 description 1
230000002363 herbicidal effect Effects 0.000 description 1
239000004009 herbicide Substances 0.000 description 1
239000000833 heterodimer Substances 0.000 description 1
238000012203 high throughput assay Methods 0.000 description 1
238000013537 high throughput screening Methods 0.000 description 1
101150113423 hisD gene Proteins 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
235000001050 hortel pimenta Nutrition 0.000 description 1
230000006658 host protein synthesis Effects 0.000 description 1
230000028996 humoral immune response Effects 0.000 description 1
210000004754 hybrid cell Anatomy 0.000 description 1
235000011167 hydrochloric acid Nutrition 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
238000004191 hydrophobic interaction chromatography Methods 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
230000005934 immune activation Effects 0.000 description 1
239000012642 immune effector Substances 0.000 description 1
229940072221 immunoglobulins Drugs 0.000 description 1
238000002991 immunohistochemical analysis Methods 0.000 description 1
230000002055 immunohistochemical effect Effects 0.000 description 1
238000011532 immunohistochemical staining Methods 0.000 description 1
238000012308 immunohistochemistry method Methods 0.000 description 1
229940121354 immunomodulator Drugs 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
150000002484 inorganic compounds Chemical class 0.000 description 1
229910010272 inorganic material Inorganic materials 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
238000002743 insertional mutagenesis Methods 0.000 description 1
230000010354 integration Effects 0.000 description 1
229940117681 interleukin-12 Drugs 0.000 description 1
229940100994 interleukin-7 Drugs 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
230000009545 invasion Effects 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
238000001155 isoelectric focusing Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
101150066555 lacZ gene Proteins 0.000 description 1
239000002523 lectin Substances 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000003446 ligand Substances 0.000 description 1
238000007834 ligase chain reaction Methods 0.000 description 1
GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
230000029226 lipidation Effects 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005249 lung adenocarcinoma Diseases 0.000 description 1
210000003810 lymphokine-activated killer cell Anatomy 0.000 description 1
230000002934 lysing effect Effects 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
229910044991 metal oxide Inorganic materials 0.000 description 1
150000004706 metal oxides Chemical group 0.000 description 1
150000002739 metals Chemical group 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
238000002493 microarray Methods 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
239000003607 modifier Substances 0.000 description 1
238000001823 molecular biology technique Methods 0.000 description 1
239000000178 monomer Substances 0.000 description 1
230000004660 morphological change Effects 0.000 description 1
230000003551 muscarinic effect Effects 0.000 description 1
239000003471 mutagenic agent Substances 0.000 description 1
231100000707 mutagenic chemical Toxicity 0.000 description 1
230000003505 mutagenic effect Effects 0.000 description 1
VELGMVLNORPMAO-JTFNWEOFSA-N n-[(e)-1-[(3r,4r,5s,6r)-5-[(2s,3r,4r,5r,6r)-5-[(2s,3r,4r,5r,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)-4-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxym Chemical compound O[C@@H]1[C@@H](O)C(OCC(NC(=O)CCCCCCCCCCCCCCCCC)C(O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 VELGMVLNORPMAO-JTFNWEOFSA-N 0.000 description 1
229950006780 n-acetylglucosamine Drugs 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
239000002077 nanosphere Substances 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
229960004927 neomycin Drugs 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
239000002853 nucleic acid probe Substances 0.000 description 1
238000001821 nucleic acid purification Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000003921 oil Substances 0.000 description 1
238000006384 oligomerization reaction Methods 0.000 description 1
238000002515 oligonucleotide synthesis Methods 0.000 description 1
229920001542 oligosaccharide Polymers 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
238000005457 optimization Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
208000004019 papillary adenocarcinoma Diseases 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
244000052769 pathogen Species 0.000 description 1
239000013610 patient sample Substances 0.000 description 1
238000012510 peptide mapping method Methods 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
210000003200 peritoneal cavity Anatomy 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
150000004633 phorbol derivatives Chemical class 0.000 description 1
239000002644 phorbol ester Substances 0.000 description 1
108010082527 phosphinothricin N-acetyltransferase Proteins 0.000 description 1
150000004713 phosphodiesters Chemical group 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003014 phosphoric acid esters Chemical class 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
238000007747 plating Methods 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
229920002627 poly(phosphazenes) Polymers 0.000 description 1
229920000058 polyacrylate Polymers 0.000 description 1
230000008488 polyadenylation Effects 0.000 description 1
229920002851 polycationic polymer Polymers 0.000 description 1
229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
235000015277 pork Nutrition 0.000 description 1
239000013641 positive control Substances 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000007639 printing Methods 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
230000002250 progressing effect Effects 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
229940021993 prophylactic vaccine Drugs 0.000 description 1
201000005825 prostate adenocarcinoma Diseases 0.000 description 1
201000001514 prostate carcinoma Diseases 0.000 description 1
210000005267 prostate cell Anatomy 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000004845 protein aggregation Effects 0.000 description 1
230000012846 protein folding Effects 0.000 description 1
230000004853 protein function Effects 0.000 description 1
239000000007 protein synthesis inhibitor Substances 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
235000021251 pulses Nutrition 0.000 description 1
239000002510 pyrogen Substances 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000003439 radiotherapeutic effect Effects 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000008439 repair process Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000000284 resting effect Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000010187 selection method Methods 0.000 description 1
230000000405 serological effect Effects 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
238000012868 site-directed mutagenesis technique Methods 0.000 description 1
239000004055 small Interfering RNA Substances 0.000 description 1
229940126586 small molecule drug Drugs 0.000 description 1
238000007921 solubility assay Methods 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
210000003802 sputum Anatomy 0.000 description 1
208000024794 sputum Diseases 0.000 description 1
230000010473 stable expression Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000010959 steel Substances 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
238000003860 storage Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000012385 systemic delivery Methods 0.000 description 1
230000008685 targeting Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
229940021747 therapeutic vaccine Drugs 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
108060008226 thioredoxin Proteins 0.000 description 1
229940094937 thioredoxin Drugs 0.000 description 1
229940113082 thymine Drugs 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
238000012090 tissue culture technique Methods 0.000 description 1
238000004448 titration Methods 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
230000005030 transcription termination Effects 0.000 description 1
238000010361 transduction Methods 0.000 description 1
230000026683 transduction Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000006276 transfer reaction Methods 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
230000010474 transient expression Effects 0.000 description 1
230000014621 translational initiation Effects 0.000 description 1
230000005945 translocation Effects 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
235000011178 triphosphate Nutrition 0.000 description 1
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
101150081616 trpB gene Proteins 0.000 description 1
101150111232 trpB-1 gene Proteins 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
150000003668 tyrosines Chemical class 0.000 description 1
239000011882 ultra-fine particle Substances 0.000 description 1
231100000402 unacceptable toxicity Toxicity 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
229940045145 uridine Drugs 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
238000002255 vaccination Methods 0.000 description 1
239000012646 vaccine adjuvant Substances 0.000 description 1
229940124931 vaccine adjuvant Drugs 0.000 description 1
210000005048 vimentin Anatomy 0.000 description 1
238000003260 vortexing Methods 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
239000009637 wintergreen oil Substances 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1