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Article ; Online: Whole protein or long peptides in therapeutic vaccination strategies, does it make a difference?

Mangsbo, Sara M

2022 Volume 23, Issue 2, Page(s) 115–117

MeSH term(s)	Humans ; Peptides/therapeutic use ; Vaccination ; Cancer Vaccines
Chemical Substances	Peptides ; Cancer Vaccines
Language	English
Publishing date	2022-12-09
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1080/14712598.2022.2156784
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Article ; Online: Bridging responses to a human telomerase reverse transcriptase-based peptide cancer vaccine candidate in a mechanism-based model.

Ibrahim, Eman I K / Ellingsen, Espen B / Mangsbo, Sara M / Friberg, Lena E

International immunopharmacology

2023 Volume 126, Page(s) 111225

Abstract: Therapeutic cancer vaccines are novel immuno-therapeutics, aiming to improve clinical outcomes with other immunotherapies. However, obstacles to their successful clinical development remain, which model-informed drug development approaches may address. ... ...

Abstract	Therapeutic cancer vaccines are novel immuno-therapeutics, aiming to improve clinical outcomes with other immunotherapies. However, obstacles to their successful clinical development remain, which model-informed drug development approaches may address. UV1 is a telomerase based therapeutic cancer vaccine candidate being investigated in phase I clinical trials for multiple indications. We developed a mechanism-based model structure, using a nonlinear mixed-effects modeling techniques, based on longitudinal tumor sizes (sum of the longest diameters, SLD), UV1-specific immunological assessment (stimulation index, SI) and overall survival (OS) data obtained from a UV1 phase I trial including non-small cell lung cancer (NSCLC) patients and a phase I/IIa trial including malignant melanoma (MM) patients. The final structure comprised a mechanistic tumor growth dynamics (TGD) model, a model describing the probability of observing a UV1-specific immune response (SI ≥ 3) and a time-to-event model for OS. The mechanistic TGD model accounted for the interplay between the vaccine peptides, immune system and tumor. The model-predicted UV1-specific effector CD4+ T cells induced tumor shrinkage with half-lives of 103 and 154 days in NSCLC and MM patients, respectively. The probability of observing a UV1-specific immune response was mainly driven by the model-predicted UV1-specific effector and memory CD4+ T cells. A high baseline SLD and a high relative increase from nadir were identified as main predictors for a reduced OS in NSCLC and MM patients, respectively. Our model predictions highlighted that additional maintenance doses, i.e. UV1 administration for longer periods, may result in more sustained tumor size shrinkage.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung ; Cancer Vaccines/therapeutic use ; Telomerase/therapeutic use ; Lung Neoplasms/pathology ; Peptides/therapeutic use ; Melanoma
Chemical Substances	Cancer Vaccines ; Telomerase (EC 2.7.7.49) ; Peptides
Language	English
Publishing date	2023-11-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2023.111225
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Article ; Online: Epitopes Displayed in a Cyclic Peptide Scaffold Bind SARS-COV-2 Antibodies.

Eriksson, Camilla / Gunasekera, Sunithi / Muhammad, Taj / Zhang, Mingshu / Laurén, Ida / Mangsbo, Sara M / Lord, Martin / Göransson, Ulf

Chembiochem : a European journal of chemical biology

2023 Volume 24, Issue 15, Page(s) e202300103

Abstract: The SARS-CoV-2 virus that causes COVID-19 is a global health issue. The spread of the virus has ... of continuous surveillance of the SARS-CoV-2 virus by using timely and accurate diagnostic tools. Here, we used ... reactive to SARS-CoV-2 antibodies. Using peptide sequences from different domains of SARS-CoV-2 spike ...

Abstract	The SARS-CoV-2 virus that causes COVID-19 is a global health issue. The spread of the virus has resulted in seven million deaths to date. The emergence of new viral strains highlights the importance of continuous surveillance of the SARS-CoV-2 virus by using timely and accurate diagnostic tools. Here, we used a stable cyclic peptide scaffolds to present antigenic sequences derived from the spike protein that are reactive to SARS-CoV-2 antibodies. Using peptide sequences from different domains of SARS-CoV-2 spike proteins, we grafted epitopes on the peptide scaffold sunflower trypsin inhibitor 1 (SFTI-1). These scaffold peptides were then used to develop an ELISA to detect SARS-CoV-2 antibodies in serum. We show that displaying epitopes on the scaffold improves reactivity overall. One of the scaffold peptides (S2_1146-1161_c) has reactivity equal to that of commercial assays, and shows diagnostic potential.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Epitopes ; Antibodies, Viral ; Peptides ; Peptides, Cyclic
Chemical Substances	Epitopes ; Antibodies, Viral ; Peptides ; Peptides, Cyclic
Language	English
Publishing date	2023-07-12
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.202300103
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Article ; Online: MALT1 inhibition suppresses antigen-specific T cell responses.

Kerzeli, Iliana K / Nasi, Aikaterini / Fletcher, Erika / Chourlia, Aikaterini / Kallin, Anders / Finnberg, Niklas / Ersmark, Karolina / Lampinen, Maria / Albertella, Mark / Öberg, Fredrik / Mangsbo, Sara M

Cellular immunology

2024 Volume 397-398, Page(s) 104814

Abstract: The aim of this study was to assess the potential use of a selective small molecule MALT1 inhibitor in solid tumor treatment as an immunotherapy targeting regulatory T-cells (Tregs). In vitro, MALT1 inhibition suppressed the proteolytic cleavage of the ... ...

Abstract	The aim of this study was to assess the potential use of a selective small molecule MALT1 inhibitor in solid tumor treatment as an immunotherapy targeting regulatory T-cells (Tregs). In vitro, MALT1 inhibition suppressed the proteolytic cleavage of the MALT1-substrate HOIL1 and blocked IL-2 secretion in Jurkat cells. It selectively suppressed the proliferation of PBMC-derived Tregs, with no effect on conventional CD4
MeSH term(s)	Animals ; Leukocytes, Mononuclear ; T-Lymphocytes, Regulatory ; CD8-Positive T-Lymphocytes ; Neoplasms ; Proteolysis
Language	English
Publishing date	2024-02-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80094-6
ISSN	1090-2163 ; 0008-8749
ISSN (online)	1090-2163
ISSN	0008-8749
DOI	10.1016/j.cellimm.2024.104814
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Article ; Online: Telomerase as a Target for Therapeutic Cancer Vaccines and Considerations for Optimizing Their Clinical Potential.

Ellingsen, Espen Basmo / Mangsbo, Sara M / Hovig, Eivind / Gaudernack, Gustav

Frontiers in immunology

2021 Volume 12, Page(s) 682492

Abstract: Telomerase-based therapeutic cancer vaccines (TCVs) have been under clinical investigation for the past two decades. Despite past failures, TCVs have gained renewed enthusiasm for their potential to improve the efficacy of checkpoint inhibition. ... ...

Abstract	Telomerase-based therapeutic cancer vaccines (TCVs) have been under clinical investigation for the past two decades. Despite past failures, TCVs have gained renewed enthusiasm for their potential to improve the efficacy of checkpoint inhibition. Telomerase stands as an attractive target for TCVs due to its almost universal presence in cancer and its essential function promoting tumor growth. Herein, we review tumor telomerase biology that may affect the efficacy of therapeutic vaccination and provide insights on optimal vaccine design and treatment combinations. Tumor types possessing mechanisms of increased telomerase expression combined with an immune permissive tumor microenvironment are expected to increase the therapeutic potential of telomerase-targeting cancer vaccines. Regardless, rational treatment combinations, such as checkpoint inhibitors, are likely necessary to bring out the true clinical potential of TCVs.
MeSH term(s)	Animals ; Biomarkers, Tumor ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Combined Modality Therapy ; Disease Management ; Disease Susceptibility ; Humans ; Immunotherapy/adverse effects ; Immunotherapy/methods ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/therapy ; Research ; Telomerase/genetics ; Telomerase/metabolism ; Tumor Microenvironment/immunology ; Vaccination
Chemical Substances	Biomarkers, Tumor ; Cancer Vaccines ; Telomerase (EC 2.7.7.49)
Language	English
Publishing date	2021-07-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.682492
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Article ; Online: Antibodies from serum and CSF of multiple sclerosis patients bind to oligodendroglial and neuronal cell-lines.

Nazir, Faisal Hayat / Wiberg, Anna / Müller, Malin / Mangsbo, Sara / Burman, Joachim

Brain communications

2023 Volume 5, Issue 3, Page(s) fcad164

Abstract: Multiple sclerosis is a highly complex and heterogeneous disease. At the onset it often presents as a clinically isolated syndrome. Thereafter relapses are followed by periods of remissions, but eventually, most patients develop secondary progressive ... ...

Abstract	Multiple sclerosis is a highly complex and heterogeneous disease. At the onset it often presents as a clinically isolated syndrome. Thereafter relapses are followed by periods of remissions, but eventually, most patients develop secondary progressive multiple sclerosis. It is widely accepted that autoantibodies are important to the pathogenesis of multiple sclerosis, but hitherto it has been difficult to identify the target of such autoantibodies. As an alternative strategy, cell-based methods of detecting autoantibodies have been developed. The objective of this study was to explore differences in the binding of antibodies from sera and CSF of multiple sclerosis patients and controls to oligodendroglial and neuronal cell-lines, related to antibody type, immunoglobulin (IgG/IgM), matrix (serum/CSF) and disease course. The oligodendroglial and neuronal cell-lines were expanded in tissue culture flasks and transferred to 96-well plates at a concentration of 50 000 cells/well followed by fixation and blocking with bovine serum albumin. Sera and CSF samples, from healthy controls and multiple sclerosis patients, were incubated with the fixed cells. Epitope binding of immunoglobulins (IgG and IgM) in sera and CSF was detected using biotinylated anti-human IgM and IgG followed by avidin conjugated to horseradish peroxidase. Horseradish peroxidase activity was detected with 3,3',5,5'-tetramethylbenzidine substrate. Serum from 76 patients and 30 controls as well as CSF from 62 patients and 32 controls were investigated in the study. The binding was similar between clinically isolated syndrome patients and controls, whereas the largest differences were observed between secondary progressive multiple sclerosis patients and controls. Antibodies from multiple sclerosis patients (all disease course combined) bound more to all investigated cell-lines, irrespectively of matrix type, but binding of immunoglobulin G from CSF to human oligodendroglioma cell-line discriminated best between multiple sclerosis patients and controls with a sensitivity of 93% and a specificity of 96%. The cell-based enzyme linked immunosorbent assay (ELISA) was able to discriminate between multiple sclerosis patients and controls with a high degree of accuracy. The disease course was the major determinant for the antibody binding.
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcad164
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Article ; Online: Tumor localized agonistic anti-CD40 therapy and beyond.

Eltahir, Mohamed / Persson, Helena / Mangsbo, Sara

Expert opinion on biological therapy

2020 Volume 20, Issue 3, Page(s) 215–217

Language	English
Publishing date	2020-01-10
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1080/14712598.2020.1713084
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Article ; Online: Symptoms and Functional Impairment Assessed 8 Months After Mild COVID-19 Among Health Care Workers.

Havervall, Sebastian / Rosell, Axel / Phillipson, Mia / Mangsbo, Sara M / Nilsson, Peter / Hober, Sophia / Thålin, Charlotte

JAMA

2021 Volume 325, Issue 19, Page(s) 2015–2016

MeSH term(s)	Adult ; COVID-19/complications ; COVID-19/diagnosis ; COVID-19 Serological Testing ; Chronic Disease ; Cohort Studies ; Female ; Health Personnel ; Humans ; Immunoglobulin G/blood ; Male ; Middle Aged ; SARS-CoV-2/immunology
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2021-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2021.5612
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Article ; Online: Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer.

Kerzeli, Iliana K / Kostakis, Alexandros / Türker, Polat / Malmström, Per-Uno / Hemdan, Tammer / Mezheyeuski, Artur / Ward, Douglas G / Bryan, Richard T / Segersten, Ulrika / Lord, Martin / Mangsbo, Sara M

BMC cancer

2023 Volume 23, Issue 1, Page(s) 605

Abstract: Background: Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient ... ...

Abstract	Background: Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required. Methods: In this study, immuno-oncology focused, multiplexed proximity extension assays were utilised to analyse plasma (n = 90) and urine (n = 40) samples from 90 newly-diagnosed and treatment-naïve bladder cancer patients. Public single-cell RNA-sequencing and microarray data from patient tumour tissues and murine OH-BBN-induced urothelial carcinomas were also explored to further corroborate the proteomic findings. Results: Plasma from muscle-invasive, urothelial bladder cancer patients displayed higher levels of MMP7 (p = 0.028) and CCL23 (p = 0.03) compared to NMIBC patients, whereas urine displayed higher levels of CD27 (p = 0.044) and CD40 (p = 0.04) in the NMIBC group by two-sided Wilcoxon rank-sum tests. Random forest survival and multivariable regression analyses identified increased MMP12 plasma levels as an independent marker (p < 0.001) associated with shorter overall survival (HR = 1.8, p < 0.001, 95% CI:1.3-2.5); this finding was validated in an independent patient OLINK cohort, but could not be established using a transcriptomic microarray dataset. Single-cell transcriptomics analyses indicated tumour-infiltrating macrophages as a putative source of MMP12. Conclusions: The measurable levels of tumour-localised, immune-cell-derived MMP12 in blood suggest MMP12 as an important biomarker that could complement histopathology-based risk stratification. As MMP12 stems from infiltrating immune cells rather than the tumor cells themselves, analyses performed on tissue biopsy material risk a biased selection of biomarkers produced by the tumour, while ignoring the surrounding microenvironment.
MeSH term(s)	Humans ; Animals ; Mice ; Matrix Metalloproteinase 12/genetics ; Proteomics ; Quality of Life ; Urinary Bladder Neoplasms ; Carcinoma, Transitional Cell ; Macrophages ; Prognosis ; Tumor Microenvironment
Chemical Substances	Matrix Metalloproteinase 12 (EC 3.4.24.65) ; MMP12 protein, human (EC 3.4.24.65)
Language	English
Publishing date	2023-06-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-023-11100-0
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Article: Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade.

Eltahir, Mohamed / Isaksson, Johan / Mattsson, Johanna Sofia Margareta / Kärre, Klas / Botling, Johan / Lord, Martin / Mangsbo, Sara M / Micke, Patrick

Cancers

2021 Volume 13, Issue 13

Abstract: Checkpoint inhibitors have been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of patients demonstrate a durable clinical response. PD-L1 scoring is currently the only biomarker measure routinely used to select ...

Abstract	Checkpoint inhibitors have been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of patients demonstrate a durable clinical response. PD-L1 scoring is currently the only biomarker measure routinely used to select patients for immunotherapy, but its predictive accuracy is modest. The aim of our study was to evaluate a proteomic assay for the analysis of patient plasma in the context of immunotherapy. Pretreatment plasma samples from 43 NSCLC patients who received anti-PD-(L)1 therapy were analyzed using a proximity extension assay (PEA) to quantify 92 different immune oncology-related proteins. The plasma protein levels were associated with clinical and histopathological parameters, as well as therapy response and survival. Unsupervised hierarchical cluster analysis revealed two patient groups with distinct protein profiles associated with high and low immune protein levels, designated as "hot" and "cold". Further supervised cluster analysis based on T-cell activation markers showed that higher levels of T-cell activation markers were associated with longer progression-free survival (PFS) (
Language	English
Publishing date	2021-06-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13133116
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