ES2548391T3 - Péptidos de cambio de marco (FSP) específicos de MSI para prevención y tratamiento del cáncer - Google Patents
Péptidos de cambio de marco (FSP) específicos de MSI para prevención y tratamiento del cáncer Download PDFInfo
- Publication number
- ES2548391T3 ES2548391T3 ES11007684.1T ES11007684T ES2548391T3 ES 2548391 T3 ES2548391 T3 ES 2548391T3 ES 11007684 T ES11007684 T ES 11007684T ES 2548391 T3 ES2548391 T3 ES 2548391T3
- Authority
- ES
- Spain
- Prior art keywords
- fsp
- peptides
- treatment
- specific framework
- cancer prevention
- 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.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract description 5
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 3
- 206010028980 Neoplasm Diseases 0.000 title 1
- 201000011510 cancer Diseases 0.000 title 1
- 230000002265 prevention Effects 0.000 title 1
- 108060000255 AIM2 Proteins 0.000 abstract description 4
- 101000837903 Homo sapiens TATA box-binding protein-associated factor RNA polymerase I subunit B Proteins 0.000 abstract description 4
- 102100024064 Interferon-inducible protein AIM2 Human genes 0.000 abstract description 4
- 102100028546 TATA box-binding protein-associated factor RNA polymerase I subunit B Human genes 0.000 abstract description 4
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- 229960005486 vaccine Drugs 0.000 abstract 1
- 206010009944 Colon cancer Diseases 0.000 description 3
- 102000004060 Transforming Growth Factor-beta Type II Receptor Human genes 0.000 description 3
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 description 3
- 101150013553 CD40 gene Proteins 0.000 description 2
- 102100028843 DNA mismatch repair protein Mlh1 Human genes 0.000 description 2
- 101000577853 Homo sapiens DNA mismatch repair protein Mlh1 Proteins 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- UZOVYGYOLBIAJR-UHFFFAOYSA-N 4-isocyanato-4'-methyldiphenylmethane Chemical compound C1=CC(C)=CC=C1CC1=CC=C(N=C=O)C=C1 UZOVYGYOLBIAJR-UHFFFAOYSA-N 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 230000028996 humoral immune response Effects 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
- 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
- 238000000034 method Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000009257 reactivity 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
-
- 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
- A61K2039/80—Vaccine for a specifically defined cancer
-
- 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
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/82—Colon
-
- 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
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/828—Stomach
-
- 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
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/836—Intestine
-
- 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
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/892—Reproductive system [uterus, ovaries, cervix, testes]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Una vacuna que contiene una combinación de péptidos de cambio de marco (FSP) específicos de MSI que comprende las secuencias de aminoácidos siguientes: NTQIKALNRGLKKKTILKKAGIGMCVKVSSIFFINKQKP (TAF1B (-1)); EIFLPKGRSNSKKKGRRNRIPAVLRTEGEPLHTPSVGMRETTGLGC (HT001 (-1)); y HSTIKVIKAKKKHREVKRTNSSQLV (AIM2 (-1)).
Description
E11007684
25-09-2015
IFN-gamma antihumanos de ratón (Mabtech, Nacka, Suecia) y bloqueados con medio que contenía suero. Las PTc (día 0, 1 x 105/pocillo) se extendieron en placas 6 veces con células B autólogas activadas con CD40 (4 x 104/pocillo, TiBc o pBc, respectivamente) como células presentadoras de antígeno en 200 μl de IMDM con 10% de suero AB humano. Los péptidos se añadieron a una concentración final de 10 μg/ml. Como control positivo, las pTc se trataron 5 con 20 nanomoles/L de 12-miristato-13-acetato de forbol en combinación con 350 nanomoles/L de ionomicina. Después de incubación durante 24 horas a 37ºC, las placas se lavaron concienzudamente, se incubaron con mAb IFN-gamma antihumano biotinilado de conejo durante 4 horas, se lavaron de nuevo y se incubaron con estreptavidina-fosfatasa alcalina durante 2 horas, seguido por un paso final de lavado. Las manchas se detectaron por incubación con NBT/BCIP (Sigma-Aldrich) durante 1 hora, se paró la reacción con agua, y, después de secado,
10 se contaron las manchas microscópicamente. Los métodos han sido descritos en detalle en Schwitalle et al., 2008.
(B) Resultados
Para examinar si las respuestas de las células T específicas de FSP eran detectables en la sangre periférica de
15 pacientes de CRC MSI-H, se realizaron análisis ELISpot. Se utilizaron como células presentadoras de antígeno pBc autólogas, que tenían expresión fuerte de mHC Clase I y Clase II y coestimuladores (CD40, CD80, y CD86) así como antígenos específicos de células B (CD19 y CD23).
Se observaron reactividades acusadas contra FSPs de nuevo diseño derivados de AIM2 (-1), HT001 (-1), TAF1B (
20 1), y TGFBR2 (-1): TAF1B(-1) NTQIKALNRGLKKKTILKKAGIGMCVKVSSIFFINKQKP HT001(-1) EIFLPKGRSNSKKKGRRNRIPAVLRTEGEPLHTPSVGMRETTGLGC AIM2(-1) HSTIKVIKAKKKHREVKRTNSSQLV TGFBR2(-1) ASPKCIMKEKKSLVRLSSCVPVALMSAMTTSSSQKNITPAILTCC
25 (las secuencias de neopéptidos están subrayadas)
Los resultados obtenidos de los pacientes (n = 8) se resumen en la Tabla 1. Los resultados representativos de ELISpot se muestran en la Figura 2.
30 Tabla 1
- Respuestas de las células T específicas de FSP contra FSPs
- ID del paciente Sin péptido TAF1B (-1) HT001 (-1) AIM2 (-1) TGFBR2 (-1)
- MSI01 4 8,17 5,83 3,5 6
- MSI02 1,5 4,83 7,33 7,17 1,2
- MSI03 11,83 28,17 31,83 23,33 10,16
- MSI04 5,5 13 14,17 11,83 8,75
- MSI05 3 7,75 16 10 2,8
- MSI06 3,17 12 12,33 13,83 5,2
- MSI07 6 17 16,83 14,5 9,33
- imagen5
- MC01 1,17 3,5 3,5 3 8
- MC02 1,67 2,83 5,83 4 3,33
- MC03 0,83 1,17 1,17 2,17 4,4
- MC04 15,17 18,83 18,67 15,17 20,75
- MC05 0,33 3,17 2,17 1,33 5,67
- MC06
- 30,5 37,83 37,8 34,83 39,5
Los números medios de mancha de análisis replicados se dan para cada péptido y se ensayan individualmente. MSI01 MSI07 -pacientes con CRC MSI-H, MC01-MC06 -portador de la mutación en la línea germinal HNPCC sana. 35
Ejemplo 2
40
6
Claims (1)
-
imagen1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11007684.1A EP2572725B1 (en) | 2011-09-21 | 2011-09-21 | MSI-specific frameshift peptides (FSP) for prevention and treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2548391T3 true ES2548391T3 (es) | 2015-10-16 |
Family
ID=44719080
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11007684.1T Active ES2548391T3 (es) | 2011-09-21 | 2011-09-21 | Péptidos de cambio de marco (FSP) específicos de MSI para prevención y tratamiento del cáncer |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP2572725B1 (es) |
| CY (1) | CY1116653T1 (es) |
| DK (1) | DK2572725T3 (es) |
| ES (1) | ES2548391T3 (es) |
| PT (1) | PT2572725E (es) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101810840B1 (ko) * | 2012-12-13 | 2017-12-20 | 루프레히트-칼스-유니페어지테트 하이델베르크 | 암의 예방 및 치료용 msi-특이적 프레임쉬프트 펩티드(fsp) |
| EP3075389A1 (en) | 2015-03-31 | 2016-10-05 | Technische Universität München | T cell receptors and peptides derived by mutations for the treatment of cancer |
| EP3630130B1 (en) | 2017-06-02 | 2022-08-31 | Arizona Board of Regents on behalf of Arizona State University | A method to create personalized cancer vaccines |
| WO2019055618A1 (en) | 2017-09-15 | 2019-03-21 | Arizona Board Of Regents On Behalf Of Arizona State University | METHODS OF CLASSIFYING RESPONSES TO ANTICANCER IMMUNOTHERAPY |
| WO2021067550A1 (en) | 2019-10-02 | 2021-04-08 | Arizona Board Of Regents On Behalf Of Arizona State University | Methods and compositions for identifying neoantigens for use in treating and preventing cancer |
| WO2021239980A2 (en) | 2020-05-28 | 2021-12-02 | Hubro Therapeutics As | A peptide cocktail |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2194761C (en) | 1994-07-15 | 2006-12-19 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
| WO2003087162A2 (en) * | 2002-04-18 | 2003-10-23 | Mtm Laboratories Ag | Neopeptides and methods useful for detection and treatment of cancer |
-
2011
- 2011-09-21 EP EP11007684.1A patent/EP2572725B1/en active Active
- 2011-09-21 PT PT110076841T patent/PT2572725E/pt unknown
- 2011-09-21 DK DK11007684.1T patent/DK2572725T3/en active
- 2011-09-21 ES ES11007684.1T patent/ES2548391T3/es active Active
-
2015
- 2015-08-26 CY CY20151100752T patent/CY1116653T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK2572725T3 (en) | 2015-09-21 |
| CY1116653T1 (el) | 2017-03-15 |
| EP2572725B1 (en) | 2015-07-08 |
| EP2572725A1 (en) | 2013-03-27 |
| PT2572725E (pt) | 2015-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2548391T3 (es) | Péptidos de cambio de marco (FSP) específicos de MSI para prevención y tratamiento del cáncer | |
| Pardi et al. | Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses | |
| Manigold et al. | Highly differentiated, resting gn-specific memory CD8+ T cells persist years after infection by andes hantavirus | |
| Gao et al. | T follicular helper 17 (Tfh17) cells are superior for immunological memory maintenance | |
| Li et al. | Infection of mouse bone marrow-derived dendritic cells by live attenuated Japanese encephalitis virus induces cells maturation and triggers T cells activation | |
| CN101942013B (zh) | 乙肝病毒核心抗原和e抗原的HLA-DR9限制性调节性T细胞表位及其应用 | |
| Fahrner et al. | The polarity and specificity of SARS-CoV2-specific T lymphocyte responses determine disease susceptibility | |
| SERNA ORTEGA | The interleukin 21 (IL 21)/microRNA-29 (miR-29) axis is associated with natural resistance to HIV-1 infection | |
| Fujitani et al. | Longitudinal analysis of B-and T-cell responses to SARS-CoV-2 recombinant S-protein vaccine S-268019-b in phase 1/2 priming and booster study | |
| Gao et al. | Type 17 Follicular Helper T (Tfh17) Cells are Superior for Memory Maintenance | |
| Beima‐Sofie et al. | MOPDA0101: Toll‐like receptor (TLR) 9 variant is associated with mother‐to‐child transmission (MTCT) of HIV‐1 and TLR9 and TLR8 variants are associated with peak viral load in HIV‐1‐positive infants | |
| Fitzgerald et al. | TUAA0105: A universal nanoparticle cell secretion capture assay for the study of HIV‐1‐positive tissues | |
| Henrich et al. | THAA0101: Long‐term reduction in peripheral blood HIV‐1 reservoirs following reduced‐intensity conditioning allogeneic stem cell transplantation in two HIV‐positive individuals | |
| Ruel et al. | THPDA0205: CXCR4‐tropism is associated with the preferential establishment of an HIV‐reservoir in naïve CD4+ T cells among HIV‐positive Ugandan children receiving antiretroviral therapy | |
| Santos‐Oliveira et al. | THPDA0102: Cytokine storm in leishmania/HIV‐1 co‐infected patients can be caused by LPS and leishmania infection | |
| Christ et al. | TUAA0301: Pre‐clinical evaluation of HIV replication inhibitors that target the HIV‐integrase‐LEDGF/p75 interaction | |
| Gonzalez et al. | TUPDA0104: Characterization of broadly neutralizing antibodies (bNAbs) to HIV‐1 present in a cohort of long term non‐progressors (LTNPs) | |
| Madrid‐Elena et al. | WEPDA0204: Maraviroc (MVC) can activate NFkB in resting CD4 T cells of patients infected with R5 or D/M HIV‐1 | |
| Palmer et al. | TUAA0104: Glut1: establishing a new paradigm for HIV‐1 infection by regulating glucose metabolism and activation in CD4+ T cells in HIV‐1‐positive subjects | |
| An et al. | MOPDA0104: ZNDR1: gene affects host susceptibility to HIV‐1 infection | |
| Vojnov et al. | MOAA0202: The majority of freshly sorted SIV‐specific CD8:+: T cells cannot suppress viral replication in SIV‐infected macrophages | |
| Kline et al. | THAA0102: Viral tissue reservoirs are determined early and little viral RNA is detected during suppression by three or four drug regimens in the macaque model | |
| Blackinton et al. | WEPDA0201: Integration of global techniques to implicate post‐transcriptional regulation in HIV infection | |
| Lifson et al. | MOLBA02: Evaluation of treatment with the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid; SAHA) in antiretroviral drug treated, SIVmac239‐infected rhesus macaques | |
| Josefsson et al. | THAA0105: Characterization of persistent HIV‐1 in a broad spectrum of CD4+ T cells isolated from peripheral blood and gut associated lymphoid tissue from patients on long‐term suppressive therapy |