CA2979676A1 - Methodes de suivi de la reponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaire - Google Patents
Methodes de suivi de la reponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaireInfo
- Publication number
- CA2979676A1 CA2979676A1 CA2979676A CA2979676A CA2979676A1 CA 2979676 A1 CA2979676 A1 CA 2979676A1 CA 2979676 A CA2979676 A CA 2979676A CA 2979676 A CA2979676 A CA 2979676A CA 2979676 A1 CA2979676 A1 CA 2979676A1
- Authority
- CA
- Canada
- Prior art keywords
- her2
- response
- cancer
- cells
- thl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000004044 response Effects 0.000 title claims abstract description 314
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 130
- 238000000034 method Methods 0.000 title claims abstract description 99
- 201000011510 cancer Diseases 0.000 title claims abstract description 66
- 238000012544 monitoring process Methods 0.000 title claims description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 276
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 249
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 231
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 143
- 238000002255 vaccination Methods 0.000 claims abstract description 58
- 102000043131 MHC class II family Human genes 0.000 claims abstract description 34
- 108091054438 MHC class II family Proteins 0.000 claims abstract description 34
- 230000000994 depressogenic effect Effects 0.000 claims abstract description 34
- 210000004366 CD4-positive T-lymphocyte Anatomy 0.000 claims abstract description 28
- 210000004443 dendritic cell Anatomy 0.000 claims abstract description 24
- 210000004369 blood Anatomy 0.000 claims abstract description 22
- 239000008280 blood Substances 0.000 claims abstract description 22
- 208000017891 HER2 positive breast carcinoma Diseases 0.000 claims abstract description 16
- 230000001093 anti-cancer Effects 0.000 claims abstract description 11
- 210000000612 antigen-presenting cell Anatomy 0.000 claims abstract description 11
- 239000002243 precursor Substances 0.000 claims abstract description 11
- 230000028327 secretion Effects 0.000 claims abstract description 5
- 230000029662 T-helper 1 type immune response Effects 0.000 claims abstract description 4
- 102000008070 Interferon-gamma Human genes 0.000 claims abstract description 3
- 108010074328 Interferon-gamma Proteins 0.000 claims abstract description 3
- 229960003130 interferon gamma Drugs 0.000 claims abstract description 3
- 229960000575 trastuzumab Drugs 0.000 claims description 104
- 238000011282 treatment Methods 0.000 claims description 72
- 208000026310 Breast neoplasm Diseases 0.000 claims description 64
- 206010006187 Breast cancer Diseases 0.000 claims description 62
- 238000002512 chemotherapy Methods 0.000 claims description 57
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 57
- 210000000481 breast Anatomy 0.000 claims description 51
- 208000030776 invasive breast carcinoma Diseases 0.000 claims description 43
- 230000001575 pathological effect Effects 0.000 claims description 42
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 27
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 claims description 23
- 238000002560 therapeutic procedure Methods 0.000 claims description 23
- 238000003556 assay Methods 0.000 claims description 20
- 238000001514 detection method Methods 0.000 claims description 18
- 238000009534 blood test Methods 0.000 claims description 16
- 210000004072 lung Anatomy 0.000 claims description 15
- 230000002163 immunogen Effects 0.000 claims description 14
- 238000001356 surgical procedure Methods 0.000 claims description 14
- 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 13
- 210000001616 monocyte Anatomy 0.000 claims description 10
- 230000004043 responsiveness Effects 0.000 claims description 9
- 230000003213 activating effect Effects 0.000 claims description 8
- 229940029030 dendritic cell vaccine Drugs 0.000 claims description 8
- 238000011275 oncology therapy Methods 0.000 claims description 8
- 210000004556 brain Anatomy 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 238000009169 immunotherapy Methods 0.000 claims description 7
- 210000004185 liver Anatomy 0.000 claims description 7
- 238000012216 screening Methods 0.000 claims description 7
- 102000004190 Enzymes Human genes 0.000 claims description 6
- 108090000790 Enzymes Proteins 0.000 claims description 6
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 claims description 6
- 230000002611 ovarian Effects 0.000 claims description 6
- 230000007170 pathology Effects 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 230000001629 suppression Effects 0.000 claims description 4
- 238000002626 targeted therapy Methods 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 201000004101 esophageal cancer Diseases 0.000 claims description 3
- 210000003238 esophagus Anatomy 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 230000002980 postoperative effect Effects 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 210000000447 Th1 cell Anatomy 0.000 claims description 2
- 238000009258 post-therapy Methods 0.000 claims description 2
- 229960005486 vaccine Drugs 0.000 abstract description 31
- 210000004027 cell Anatomy 0.000 description 183
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 164
- 230000001186 cumulative effect Effects 0.000 description 60
- 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 description 58
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 58
- 239000002671 adjuvant Substances 0.000 description 45
- 230000036039 immunity Effects 0.000 description 43
- 230000028993 immune response Effects 0.000 description 39
- 102000015694 estrogen receptors Human genes 0.000 description 33
- 108010038795 estrogen receptors Proteins 0.000 description 33
- 239000000427 antigen Substances 0.000 description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 31
- 108091007433 antigens Proteins 0.000 description 30
- 102000036639 antigens Human genes 0.000 description 30
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 28
- 102100040247 Tumor necrosis factor Human genes 0.000 description 28
- 230000006907 apoptotic process Effects 0.000 description 28
- 201000010099 disease Diseases 0.000 description 27
- 238000012360 testing method Methods 0.000 description 26
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 description 24
- 201000007273 ductal carcinoma in situ Diseases 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 23
- 102000004127 Cytokines Human genes 0.000 description 21
- 108090000695 Cytokines Proteins 0.000 description 21
- 231100000504 carcinogenesis Toxicity 0.000 description 21
- 238000004519 manufacturing process Methods 0.000 description 21
- 208000005623 Carcinogenesis Diseases 0.000 description 20
- 235000001014 amino acid Nutrition 0.000 description 20
- 230000036952 cancer formation Effects 0.000 description 20
- 238000002595 magnetic resonance imaging Methods 0.000 description 18
- 150000007523 nucleic acids Chemical class 0.000 description 18
- 229940024606 amino acid Drugs 0.000 description 17
- 230000003053 immunization Effects 0.000 description 17
- 238000002649 immunization Methods 0.000 description 17
- 102000039446 nucleic acids Human genes 0.000 description 17
- 108020004707 nucleic acids Proteins 0.000 description 17
- 230000001965 increasing effect Effects 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 15
- 230000003902 lesion Effects 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 230000009257 reactivity Effects 0.000 description 15
- 238000010186 staining Methods 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 14
- 230000000875 corresponding effect Effects 0.000 description 13
- 230000031261 interleukin-10 production Effects 0.000 description 13
- 230000009885 systemic effect Effects 0.000 description 13
- 238000001262 western blot Methods 0.000 description 13
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 12
- 108091006116 chimeric peptides Proteins 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 229960002087 pertuzumab Drugs 0.000 description 12
- 230000035945 sensitivity Effects 0.000 description 12
- 238000011460 HER2-targeted therapy Methods 0.000 description 11
- 230000004048 modification Effects 0.000 description 11
- 238000012986 modification Methods 0.000 description 11
- 210000000988 bone and bone Anatomy 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000000684 flow cytometry Methods 0.000 description 10
- 238000002509 fluorescent in situ hybridization Methods 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 230000000750 progressive effect Effects 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 238000006467 substitution reaction Methods 0.000 description 10
- 102000003952 Caspase 3 Human genes 0.000 description 9
- 108090000397 Caspase 3 Proteins 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 230000006735 deficit Effects 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 210000002443 helper t lymphocyte Anatomy 0.000 description 9
- 230000001506 immunosuppresive effect Effects 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 230000002018 overexpression Effects 0.000 description 9
- 239000013641 positive control Substances 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 8
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 8
- 102000003970 Vinculin Human genes 0.000 description 8
- 108090000384 Vinculin Proteins 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 238000003745 diagnosis Methods 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 101150029707 ERBB2 gene Proteins 0.000 description 7
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 7
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 7
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 7
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 7
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 7
- 238000007792 addition Methods 0.000 description 7
- 230000001640 apoptogenic effect Effects 0.000 description 7
- 210000003719 b-lymphocyte Anatomy 0.000 description 7
- 238000003501 co-culture Methods 0.000 description 7
- 230000001276 controlling effect Effects 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 7
- 238000011502 immune monitoring Methods 0.000 description 7
- 102000040430 polynucleotide Human genes 0.000 description 7
- 108091033319 polynucleotide Proteins 0.000 description 7
- 239000002157 polynucleotide Substances 0.000 description 7
- 230000000306 recurrent effect Effects 0.000 description 7
- 230000008685 targeting Effects 0.000 description 7
- 231100000588 tumorigenic Toxicity 0.000 description 7
- 230000000381 tumorigenic effect Effects 0.000 description 7
- 102000001301 EGF receptor Human genes 0.000 description 6
- 238000011510 Elispot assay Methods 0.000 description 6
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 6
- 241001529936 Murinae Species 0.000 description 6
- 238000001994 activation Methods 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 6
- 229960004891 lapatinib Drugs 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 210000004985 myeloid-derived suppressor cell Anatomy 0.000 description 6
- 238000009099 neoadjuvant therapy Methods 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 210000003289 regulatory T cell Anatomy 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 229960000814 tetanus toxoid Drugs 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 239000013598 vector Substances 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 5
- 241000222122 Candida albicans Species 0.000 description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 5
- 206010061819 Disease recurrence Diseases 0.000 description 5
- 101001066288 Gallus gallus GATA-binding factor 3 Proteins 0.000 description 5
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 5
- 101000713602 Homo sapiens T-box transcription factor TBX21 Proteins 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 5
- 230000017274 T cell anergy Effects 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- 102100036840 T-box transcription factor TBX21 Human genes 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000000090 biomarker Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 229940095731 candida albicans Drugs 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 108091008039 hormone receptors Proteins 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 230000035935 pregnancy Effects 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 5
- 238000002271 resection Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 4
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 4
- 229930012538 Paclitaxel Natural products 0.000 description 4
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 4
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 4
- 229940009456 adriamycin Drugs 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 229940022353 herceptin Drugs 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000007477 logistic regression Methods 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 230000000527 lymphocytic effect Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 238000011227 neoadjuvant chemotherapy Methods 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 238000009021 pre-vaccination Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 102000003998 progesterone receptors Human genes 0.000 description 4
- 108090000468 progesterone receptors Proteins 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 4
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 4
- 238000000116 DAPI staining Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 3
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 3
- 102100022338 Integrin alpha-M Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 230000003190 augmentative effect Effects 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 238000011393 cytotoxic chemotherapy Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 239000003547 immunosorbent Substances 0.000 description 3
- 230000006882 induction of apoptosis Effects 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000001565 modulated differential scanning calorimetry Methods 0.000 description 3
- 230000008823 permeabilization Effects 0.000 description 3
- 230000002516 postimmunization Effects 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000011301 standard therapy Methods 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000002123 temporal effect Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- AHOKKYCUWBLDST-QYULHYBRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2,6-diaminohexanoyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)[C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=CC=C1 AHOKKYCUWBLDST-QYULHYBRSA-N 0.000 description 2
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 2
- 229940122815 Aromatase inhibitor Drugs 0.000 description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 150000008574 D-amino acids Chemical class 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 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
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 2
- 206010043376 Tetanus Diseases 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 206010066901 Treatment failure Diseases 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 239000003886 aromatase inhibitor Substances 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 208000011803 breast fibrocystic disease Diseases 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005138 cryopreservation Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000000432 density-gradient centrifugation Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000009093 first-line therapy Methods 0.000 description 2
- 238000002124 flame ionisation detection Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000017307 interleukin-4 production Effects 0.000 description 2
- 238000010212 intracellular staining Methods 0.000 description 2
- 230000006651 lactation Effects 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 230000009397 lymphovascular invasion Effects 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 229940023041 peptide vaccine Drugs 0.000 description 2
- 235000020030 perry Nutrition 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 230000001023 pro-angiogenic effect Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- -1 serine and threonine Chemical class 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000004808 supercritical fluid chromatography Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940063683 taxotere Drugs 0.000 description 2
- 239000003970 toll like receptor agonist Substances 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- 230000002476 tumorcidal effect Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- ILBKBRBXCXDCFB-UHFFFAOYSA-N 4-(1h-indol-2-yl)benzene-1,3-diamine Chemical compound NC1=CC(N)=CC=C1C1=CC2=CC=CC=C2N1 ILBKBRBXCXDCFB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-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
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 229940124297 CDK 4/6 inhibitor Drugs 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241001622623 Coeliadinae Species 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 108010055196 EphA2 Receptor Proteins 0.000 description 1
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- 210000000712 G cell Anatomy 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 1
- 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 description 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 description 1
- 101001005722 Homo sapiens Melanoma-associated antigen 6 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 150000008575 L-amino acids Chemical class 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 102100025075 Melanoma-associated antigen 6 Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 241000840267 Moma Species 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 101100514733 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) mri-1 gene Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 101710176384 Peptide 1 Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 229940123384 Toll-like receptor (TLR) agonist Drugs 0.000 description 1
- 101710149792 Triosephosphate isomerase, chloroplastic Proteins 0.000 description 1
- 101710195516 Triosephosphate isomerase, glycosomal Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 210000002769 b effector cell Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 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 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 1
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000013501 data transformation Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000009110 definitive therapy Methods 0.000 description 1
- 238000013154 diagnostic monitoring Methods 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 210000001808 exosome Anatomy 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000012953 feeding on blood of other organism Effects 0.000 description 1
- ZNOLGFHPUIJIMJ-UHFFFAOYSA-N fenitrothion Chemical compound COP(=S)(OC)OC1=CC=C([N+]([O-])=O)C(C)=C1 ZNOLGFHPUIJIMJ-UHFFFAOYSA-N 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000051957 human ERBB2 Human genes 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000008102 immune modulation Effects 0.000 description 1
- 238000011493 immune profiling Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 208000026535 luminal A breast carcinoma Diseases 0.000 description 1
- 208000026534 luminal B breast carcinoma Diseases 0.000 description 1
- 208000024923 lung germ cell tumor Diseases 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000009607 mammography Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000001558 permutation test Methods 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 238000011248 postoperative chemotherapy Methods 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 210000001243 pseudopodia Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000009118 salvage therapy Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- CBHOWTTXCQAOID-UHFFFAOYSA-L sodium ethane formaldehyde mercury(2+) molecular iodine 2-sulfidobenzoate Chemical class [Na+].[Hg++].C[CH2-].II.C=O.[O-]C(=O)c1ccccc1[S-] CBHOWTTXCQAOID-UHFFFAOYSA-L 0.000 description 1
- VIDRYROWYFWGSY-UHFFFAOYSA-N sotalol hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 VIDRYROWYFWGSY-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 101150050362 thl gene Proteins 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- 231100000048 toxicity data Toxicity 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/001106—Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464403—Receptors for growth factors
- A61K39/464406—Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57419—Specifically defined cancers of colon
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/555—Interferons [IFN]
- G01N2333/57—IFN-gamma
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/54—Determining the risk of relapse
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Developmental Biology & Embryology (AREA)
Abstract
La présente invention concerne une méthode de diagnostic ou de traitement d'un sujet mammifère souffrant ou risquant de souffrir d'un cancer, comprenant les étapes consistant à générer une réponse lymphocytaire impliquant des lymphocytes Th1 CD4+ circulants anticancéreux à partir de cellules présentatrices d'antigènes ou de leurs précurseurs et des lymphocytes T CD4+ à partir d'un échantillon de sang dudit sujet qui provoque la sécrétion d'interféron-gamma (« IFN-? ») ; et à détecter ladite réponse lymphocytaire Th1 CD4+ anticancéreuse pour déterminer si ladite réponse est minorée. La présente invention concerne un procédé de restauration de la réponse immunitaire lymphocytaire Th1 CD4+ spécifique de HER2 chez un patient atteint d'un cancer du sein HER2-positif en ayant besoin. Ledit procédé comprend les étapes consistant à administrer au dit patient une quantité thérapeutiquement efficace d'un vaccin à base de cellules dendritiques (« CD ») comprenant des cellules dendritiques autologues pulsées avec des peptides de liaison du CMH de classe II dérivés de HER2 (« vaccination CD ») afin de renforcer la réponse lymphocytaire Th1 CD4+ anti-HER2 chez ledit patient ; et mesurer ladite réponse Th1 anti-HER2 chez ledit patient avant et après la vaccination CD pour déterminer l'ampleur du renforcement de ladite réponse.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| WOPCT/US2015/020613 | 2015-03-13 | ||
| US14/658,095 | 2015-03-13 | ||
| US14/658,095 US20150323547A1 (en) | 2014-03-14 | 2015-03-13 | Methods for monitoring cd4+ t-helper type 1 response in cancer and immune restoration |
| PCT/US2015/020613 WO2015139003A1 (fr) | 2014-03-14 | 2015-03-13 | Méthodes de suivi de la réponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaire |
| US14/985,303 | 2015-12-30 | ||
| US14/985,303 US20160252511A1 (en) | 2014-03-14 | 2015-12-30 | Methods for monitoring cd4+ t-helper type 1 response in cancer and immune restoration |
| PCT/US2016/020987 WO2016153761A1 (fr) | 2015-03-13 | 2016-03-04 | Méthodes de suivi de la réponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaire |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2979676A1 true CA2979676A1 (fr) | 2016-09-29 |
Family
ID=56978584
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2979676A Abandoned CA2979676A1 (fr) | 2015-03-13 | 2016-03-04 | Methodes de suivi de la reponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaire |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2018515742A (fr) |
| CN (1) | CN107533065A (fr) |
| CA (1) | CA2979676A1 (fr) |
| WO (1) | WO2016153761A1 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016190940A1 (fr) * | 2015-05-22 | 2016-12-01 | Czerniecki Brian J | Fabrication de vaccins multidoses prêts à injecter à base de cellules dendritiques |
| CN117054649A (zh) * | 2023-08-04 | 2023-11-14 | 广州中医药大学第一附属医院 | 一种慢性萎缩性胃炎向胃癌转化标志物及其应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5801005A (en) * | 1993-03-17 | 1998-09-01 | University Of Washington | Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated |
| FR2891462B1 (fr) * | 2005-09-30 | 2009-10-16 | Commissariat Energie Atomique | Epitopes t cd4+ de la survivine et leurs applications |
| CN102933228A (zh) | 2010-03-15 | 2013-02-13 | 宾夕法尼亚大学董事会 | 制备和储存活化的、成熟树突细胞的体系和方法 |
| JP6255593B2 (ja) * | 2012-07-10 | 2018-01-10 | オンコセラピー・サイエンス株式会社 | Ｔｈ１細胞のＣＤＣＡ１エピトープペプチドおよびこれを含有するワクチン |
| CA2942721A1 (fr) * | 2014-03-14 | 2015-09-17 | Czerniecki, Brian J. | Methodes de suivi de la reponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaire |
-
2016
- 2016-03-04 CA CA2979676A patent/CA2979676A1/fr not_active Abandoned
- 2016-03-04 JP JP2016558088A patent/JP2018515742A/ja active Pending
- 2016-03-04 WO PCT/US2016/020987 patent/WO2016153761A1/fr active Application Filing
- 2016-03-04 CN CN201680001416.2A patent/CN107533065A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2018515742A (ja) | 2018-06-14 |
| CN107533065A (zh) | 2018-01-02 |
| WO2016153761A1 (fr) | 2016-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Galon et al. | Tumor immunology and tumor evolution: intertwined histories | |
| Spranger et al. | Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy | |
| Melero et al. | Evolving synergistic combinations of targeted immunotherapies to combat cancer | |
| US10792349B2 (en) | Galectin-3 as immunological target | |
| US20150118244A1 (en) | Anti-tumor antibodies as predictive or prognostic biomarkers of efficacy and survival in ipilimumab-treated patients | |
| Diefenbach et al. | Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission | |
| Datta et al. | Progressive loss of anti-HER2 CD4+ T-helper type 1 response in breast tumorigenesis and the potential for immune restoration | |
| Kwek et al. | Unmasking the immune recognition of prostate cancer with CTLA4 blockade | |
| JP2019524692A (ja) | Ｎａｎｔ癌ワクチン | |
| JP2022088665A (ja) | がんの治療 | |
| Fracol et al. | Response to HER-2 pulsed DC1 vaccines is predicted by both HER-2 and estrogen receptor expression in DCIS | |
| JP2007527225A (ja) | Ｅｐｈａ２ｔ−細胞エピトープアゴニストおよびその使用 | |
| JP2020124193A (ja) | 癌のｃｄ４＋ｔヘルパー１型応答の監視方法および免疫回復 | |
| Bilusic et al. | Immunotherapy in prostate cancer: emerging strategies against a formidable foe | |
| TW202210084A (zh) | Cd30陽性癌症之治療 | |
| AU2013357239B2 (en) | Novel MHC-independent tumor-associated antigens | |
| US20170261508A1 (en) | Methods for monitoring cd4+ t-helper type 1 response in cancer and immune restoration | |
| US20160252511A1 (en) | Methods for monitoring cd4+ t-helper type 1 response in cancer and immune restoration | |
| CA2979676A1 (fr) | Methodes de suivi de la reponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaire | |
| AU2016244182B2 (en) | Methods for monitoring cd4+ t-helper type 1 response in cancer and immune restoration | |
| EP3268464A1 (fr) | Méthodes de suivi de la réponse lymphocytaire impliquant des lymphocytes t auxiliaires cd4+ de type 1 dans le cancer et la reconstitution immunitaire | |
| Karyampudi et al. | A degenerate HLA-DR epitope pool of HER-2/neu reveals a novel in vivo immunodominant epitope, HER-2/neu88-102 | |
| Jung et al. | Yeast-based identification of prostate tumor antigens provides an effective vaccine platform | |
| WO2024083867A1 (fr) | Biomarqueur | |
| Currenti et al. | Immunosuppressive mechanisms of oncofetal reprogramming in the tumor microenvironment: implications in immunotherapy response |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210304 |
|
| EEER | Examination request |
Effective date: 20210304 |
|
| EEER | Examination request |
Effective date: 20210304 |
|
| FZDE | Discontinued |
Effective date: 20230707 |