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Article ; Online: mRNA Vaccines against SARS-CoV-2: Advantages and Caveats.

Echaide, Miriam / Chocarro de Erauso, Luisa / Bocanegra, Ana / Blanco, Ester / Kochan, Grazyna / Escors, David

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: The application of BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 infection has constituted a determinant resource to control the COVID-19 pandemic. Since the beginning of 2021, millions of doses have been administered in several countries of North ... ...

Abstract	The application of BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 infection has constituted a determinant resource to control the COVID-19 pandemic. Since the beginning of 2021, millions of doses have been administered in several countries of North and South America and Europe. Many studies have confirmed the efficacy of these vaccines in a wide range of ages and in vulnerable groups of people against COVID-19. Nevertheless, the emergence and selection of new variants have led to a progressive decay in vaccine efficacy. Pfizer-BioNTech and Moderna developed updated bivalent vaccines-Comirnaty and Spikevax-to improve responses against the SARS-CoV-2 Omicron variants. Frequent booster doses with monovalent or bivalent mRNA vaccines, the emergence of some rare but serious adverse events and the activation of T-helper 17 responses suggest the need for improved mRNA vaccine formulations or the use of other types of vaccines. In this review, we discuss the advantages and limitations of mRNA vaccines targeting SARS-CoV-2 focusing on the most recent, related publications.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/prevention & control ; COVID-19 Vaccines ; BNT162 Vaccine ; Pandemics ; mRNA Vaccines ; Vaccines, Combined
Chemical Substances	COVID-19 Vaccines ; BNT162 Vaccine ; mRNA Vaccines ; Vaccines, Combined
Language	English
Publishing date	2023-03-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065944
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Oleuropein-driven reprogramming of the myeloid cell compartment to sensitise tumours to PD-1/PD-L1 blockade strategies.

Blanco, Ester / Silva-Pilipich, Noelia / Bocanegra, Ana / Chocarro, Luisa / Procopio, Antonio / Ausín, Karina / Fernandez-Irigoyen, Joaquín / Fernández, Leticia / Razquin, Nerea / Igea, Ana / Garnica, Maider / Echaide, Miriam / Arasanz, Hugo / Vera, Ruth / Escors, David / Smerdou, Cristian / Kochan, Grazyna

British journal of cancer

2024 Volume 130, Issue 5, Page(s) 869–879

Abstract: Background: Previous studies have shown that functional systemic immunity is required for the efficacy of PD-1/PD-L1 blockade immunotherapies in cancer. Hence, systemic reprogramming of immunosuppressive dysfunctional myeloid cells could overcome ... ...

Abstract	Background: Previous studies have shown that functional systemic immunity is required for the efficacy of PD-1/PD-L1 blockade immunotherapies in cancer. Hence, systemic reprogramming of immunosuppressive dysfunctional myeloid cells could overcome resistance to cancer immunotherapy. Methods: Reprogramming of tumour-associated myeloid cells with oleuropein was studied by quantitative differential proteomics, phenotypic and functional assays in mice and lung cancer patients. Combinations of oleuropein and two different delivery methods of anti-PD-1 antibodies were tested in colorectal cancer tumour models and in immunotherapy-resistant lung cancer models. Results: Oleuropein treatment reprogrammed monocytic and granulocytic myeloid-derived suppressor cells, and tumour-associated macrophages towards differentiation of immunostimulatory subsets. Oleuropein regulated major differentiation programmes associated to immune modulation in myeloid cells, which potentiated T cell responses and PD-1 blockade. PD-1 antibodies were delivered by two different strategies, either systemically or expressed within tumours using a self-amplifying RNA vector. Combination anti-PD-1 therapies with oleuropein increased tumour infiltration by immunostimulatory dendritic cells in draining lymph nodes, leading to systemic antitumour T cell responses. Potent therapeutic activities were achieved in colon cancer and lung cancer models resistant to immunotherapies, even leading to complete tumour regression. Discussion: Oleuropein significantly improves the outcome of PD-1/PD-L1 blockade immunotherapy strategies by reprogramming myeloid cells.
MeSH term(s)	Humans ; Animals ; Mice ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Immune Checkpoint Inhibitors/pharmacology ; Myeloid Cells ; Immunotherapy ; Lung Neoplasms/drug therapy ; Tumor Microenvironment ; Iridoid Glucosides
Chemical Substances	B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; oleuropein (2O4553545L) ; Immune Checkpoint Inhibitors ; Iridoid Glucosides
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02561-y
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Article ; Online: Leading Edge: Intratumor Delivery of Monoclonal Antibodies for the Treatment of Solid Tumors.

Blanco, Ester / Chocarro, Luisa / Fernández-Rubio, Leticia / Bocanegra, Ana / Arasanz, Hugo / Echaide, Miriam / Garnica, Maider / Piñeiro-Hermida, Sergio / Kochan, Grazyna / Escors, David

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Immunotherapies based on immune checkpoint blockade have shown remarkable clinical outcomes and durable responses in patients with many tumor types. Nevertheless, these therapies lack efficacy in most cancer patients, even causing severe adverse events ... ...

Abstract	Immunotherapies based on immune checkpoint blockade have shown remarkable clinical outcomes and durable responses in patients with many tumor types. Nevertheless, these therapies lack efficacy in most cancer patients, even causing severe adverse events in a small subset of patients, such as inflammatory disorders and hyper-progressive disease. To diminish the risk of developing serious toxicities, intratumor delivery of monoclonal antibodies could be a solution. Encouraging results have been shown in both preclinical and clinical studies. Thus, intratumor immunotherapy as a new strategy may retain efficacy while increasing safety. This approach is still an exploratory frontier in cancer research and opens up new possibilities for next-generation personalized medicine. Local intratumor delivery can be achieved through many means, but an attractive approach is the use of gene therapy vectors expressing mAbs inside the tumor mass. Here, we summarize basic, translational, and clinical results of intratumor mAb delivery, together with descriptions of non-viral and viral strategies for mAb delivery in preclinical and clinical development. Currently, this is an expanding research subject that will surely play a key role in the future of oncology.
MeSH term(s)	Humans ; Antibodies, Monoclonal/therapeutic use ; Neoplasms/drug therapy ; Immunotherapy/methods ; Precision Medicine
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2023-01-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032676
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Article ; Online: Current Indications and Future Landscape of Bispecific Antibodies for the Treatment of Lung Cancer.

Arasanz, Hugo / Chocarro, Luisa / Fernández-Rubio, Leticia / Blanco, Ester / Bocanegra, Ana / Echaide, Miriam / Labiano, Ibone / Huerta, Ana Elsa / Alsina, Maria / Vera, Ruth / Escors, David / Kochan, Grazyna

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: Bispecific antibodies are a promising type of therapy for the treatment of cancer due to their ability to simultaneously inhibit different proteins playing a role in cancer progression. The development in lung cancer has been singularly intense because ... ...

Abstract	Bispecific antibodies are a promising type of therapy for the treatment of cancer due to their ability to simultaneously inhibit different proteins playing a role in cancer progression. The development in lung cancer has been singularly intense because of the increasingly vast knowledge of the underlying molecular routes, in particular, in oncogene-driven tumors. In this review, we present the current landscape of bispecific antibodies for the treatment of lung cancer and discuss potential scenarios where the role of these therapeutics might expand in the near future.
MeSH term(s)	Humans ; Antibodies, Bispecific/therapeutic use ; Lung Neoplasms/pathology ; Immunotherapy
Chemical Substances	Antibodies, Bispecific
Language	English
Publishing date	2023-06-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24129855
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Article ; Online: Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions.

Lachén-Montes, Mercedes / Mendizuri, Naroa / Ausín, Karina / Echaide, Miriam / Blanco, Ester / Chocarro, Luisa / de Toro, María / Escors, David / Fernández-Irigoyen, Joaquín / Kochan, Grazyna / Santamaría, Enrique

Frontiers in immunology

2022 Volume 13, Page(s) 866564

Abstract: One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at ... ...

Abstract	One of the most common symptoms in COVID-19 is a sudden loss of smell. SARS-CoV-2 has been detected in the olfactory bulb (OB) from animal models and sporadically in COVID-19 patients. To decipher the specific role over the SARS-CoV-2 proteome at olfactory level, we characterized the in-depth molecular imbalance induced by the expression of GFP-tagged SARS-CoV-2 structural proteins (M, N, E, S) on mouse OB cells. Transcriptomic and proteomic trajectories uncovered a widespread metabolic remodeling commonly converging in extracellular matrix organization, lipid metabolism and signaling by receptor tyrosine kinases. The molecular singularities and specific interactome expression modules were also characterized for each viral structural factor. The intracellular molecular imbalance induced by each SARS-CoV-2 structural protein was accompanied by differential activation dynamics in survival and immunological routes in parallel with a differentiated secretion profile of chemokines in OB cells. Machine learning through a proteotranscriptomic data integration uncovered TGF-beta signaling as a confluent activation node by the SARS-CoV-2 structural proteome. Taken together, these data provide important avenues for understanding the multifunctional immunomodulatory properties of SARS-CoV-2 M, N, S and E proteins beyond their intrinsic role in virion formation, deciphering mechanistic clues to the olfactory inflammation observed in COVID-19 patients.
MeSH term(s)	Animals ; COVID-19 ; Mice ; Protein-Tyrosine Kinases ; Proteome ; Proteomics ; SARS-CoV-2 ; Transforming Growth Factor beta
Chemical Substances	Proteome ; Transforming Growth Factor beta ; Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2022-09-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.866564
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Article: Cutting-Edge CAR Engineering: Beyond T Cells.

Chocarro, Luisa / Blanco, Ester / Fernández-Rubio, Leticia / Arasanz, Hugo / Bocanegra, Ana / Echaide, Miriam / Garnica, Maider / Ramos, Pablo / Piñeiro-Hermida, Sergio / Vera, Ruth / Kochan, Grazyna / Escors, David

Biomedicines

2022 Volume 10, Issue 12

Abstract: Chimeric antigen receptor (CAR)-T adoptive cell therapy is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in haematological malignancies. However, it still lacks efficacy in solid tumours, possibly ... ...

Abstract	Chimeric antigen receptor (CAR)-T adoptive cell therapy is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in haematological malignancies. However, it still lacks efficacy in solid tumours, possibly because engineered T cells become inactive within the immunosuppressive tumour microenvironment (TME). In the TME, cells of the myeloid lineage (M) are among the immunosuppressive cell types with the highest tumour infiltration rate. These cells interact with other immune cells, mediating immunosuppression and promoting angiogenesis. Recently, the development of CAR-M cell therapies has been put forward as a new candidate immunotherapy with good efficacy potential. This alternative CAR strategy may increase the efficacy, survival, persistence, and safety of CAR treatments in solid tumours. This remains a critical frontier in cancer research and opens up a new possibility for next-generation personalised medicine to overcome TME resistance. However, the exact mechanisms of action of CAR-M and their effect on the TME remain poorly understood. Here, we summarise the basic, translational, and clinical results of CAR-innate immune cells and CAR-M cell immunotherapies, from their engineering and mechanistic studies to preclinical and clinical development.
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10123035
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Article ; Online: Cutting-Edge: Preclinical and Clinical Development of the First Approved Lag-3 Inhibitor.

Chocarro, Luisa / Bocanegra, Ana / Blanco, Ester / Fernández-Rubio, Leticia / Arasanz, Hugo / Echaide, Miriam / Garnica, Maider / Ramos, Pablo / Piñeiro-Hermida, Sergio / Vera, Ruth / Escors, David / Kochan, Grazyna

Cells

2022 Volume 11, Issue 15

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized medical practice in oncology since the FDA approval of the first ICI 11 years ago. In light of this, Lymphocyte-Activation Gene 3 (LAG-3) is one of the most important next-generation immune ... ...

Abstract	Immune checkpoint inhibitors (ICIs) have revolutionized medical practice in oncology since the FDA approval of the first ICI 11 years ago. In light of this, Lymphocyte-Activation Gene 3 (LAG-3) is one of the most important next-generation immune checkpoint molecules, playing a similar role as Programmed cell Death protein 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4). 19 LAG-3 targeting molecules are being evaluated at 108 clinical trials which are demonstrating positive results, including promising bispecific molecules targeting LAG-3 simultaneously with other ICIs. Recently, a new dual anti-PD-1 (Nivolumab) and anti-LAG-3 (Relatimab) treatment developed by Bristol Myers Squibb (Opdualag), was approved by the Food and Drug Administration (FDA) as the first LAG-3 blocking antibody combination for unresectable or metastatic melanoma. This novel immunotherapy combination more than doubled median progression-free survival (PFS) when compared to nivolumab monotherapy (10.1 months versus 4.6 months). Here, we analyze the large clinical trial responsible for this historical approval (RELATIVITY-047), and discuss the preclinical and clinical developments that led to its jump into clinical practice. We will also summarize results achieved by other LAG-3 targeting molecules with promising anti-tumor activities currently under clinical development in phases I, I/II, II, and III. Opdualag will boost the entry of more LAG-3 targeting molecules into clinical practice, supporting the accumulating evidence highlighting the pivotal role of LAG-3 in cancer.
MeSH term(s)	Humans ; Immunologic Factors/therapeutic use ; Immunotherapy/methods ; Melanoma/drug therapy ; Nivolumab/therapeutic use
Chemical Substances	Immunologic Factors ; Nivolumab (31YO63LBSN)
Language	English
Publishing date	2022-07-30
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11152351
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Article: Immune Profiling Uncovers Memory T-Cell Responses with a Th17 Signature in Cancer Patients with Previous SARS-CoV-2 Infection Followed by mRNA Vaccination.

Echaide, Miriam / Labiano, Ibone / Delgado, Marina / Fernández de Lascoiti, Angela / Ochoa, Patricia / Garnica, Maider / Ramos, Pablo / Chocarro, Luisa / Fernández, Leticia / Arasanz, Hugo / Bocanegra, Ana / Blanco, Ester / Piñeiro-Hermida, Sergio / Morente, Pilar / Vera, Ruth / Alsina, Maria / Escors, David / Kochan, Grazyna

Cancers

2022 Volume 14, Issue 18

Abstract: It is unclear whether patients with cancer present inherently impaired responses to COVID-19 and vaccination due to their treatments, neoplastic diseases or both. To address this question, immune profiling was performed in three cohorts of healthy donors ...

Abstract	It is unclear whether patients with cancer present inherently impaired responses to COVID-19 and vaccination due to their treatments, neoplastic diseases or both. To address this question, immune profiling was performed in three cohorts of healthy donors and oncologic patients: infected with SARS-CoV-2, BNT162b2-vaccinated, and with previous COVID-19 disease and subsequently vaccinated. Cancer patients showed good antibody responses to vaccination, but poor induction of T-cell responses towards the S protein when compared to infection. Following natural infection, the major targets for T-cells were the SARS-CoV-2 structural proteins M and S, but not the N protein. Similar to antibody titers, the T-cell responses quickly decayed after six months post-vaccination. Significant memory T-cell expansion was observed in vaccinated donors only if previously diagnosed with COVID-19 before undergoing vaccination. Oncologic patients with previous COVID-19 followed by vaccination exhibited potent IL-17+ CD4 and CD8 T-cell responses and elevated numbers of circulating neutrophils in peripheral blood.
Language	English
Publishing date	2022-09-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14184464
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Article: CAR-T Cells for the Treatment of Lung Cancer.

Chocarro, Luisa / Arasanz, Hugo / Fernández-Rubio, Leticia / Blanco, Ester / Echaide, Miriam / Bocanegra, Ana / Teijeira, Lucía / Garnica, Maider / Morilla, Idoia / Martínez-Aguillo, Maite / Piñeiro-Hermida, Sergio / Ramos, Pablo / Lasarte, Juan José / Vera, Ruth / Kochan, Grazyna / Escors, David

Life (Basel, Switzerland)

2022 Volume 12, Issue 4

Abstract: Adoptive cell therapy with genetically modified T lymphocytes that express chimeric antigen receptors (CAR-T) is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in hematological malignancies. However, ...

Abstract	Adoptive cell therapy with genetically modified T lymphocytes that express chimeric antigen receptors (CAR-T) is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in hematological malignancies. However, the efficacy of CAR-T cells in solid tumors is still very unsatisfactory, because of the strong immunosuppressive tumor microenvironment that hinders immune responses. The development of next-generation personalized CAR-T cells against solid tumors is a clinical necessity. The identification of therapeutic targets for new CAR-T therapies to increase the efficacy, survival, persistence, and safety in solid tumors remains a critical frontier in cancer immunotherapy. Here, we summarize basic, translational, and clinical results of CAR-T cell immunotherapies in lung cancer, from their molecular engineering and mechanistic studies to preclinical and clinical development.
Language	English
Publishing date	2022-04-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12040561
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Article ; Online: Understanding LAG-3 Signaling.

Chocarro, Luisa / Blanco, Ester / Zuazo, Miren / Arasanz, Hugo / Bocanegra, Ana / Fernández-Rubio, Leticia / Morente, Pilar / Fernández-Hinojal, Gonzalo / Echaide, Miriam / Garnica, Maider / Ramos, Pablo / Vera, Ruth / Kochan, Grazyna / Escors, David

International journal of molecular sciences

2021 Volume 22, Issue 10

Abstract: Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune ... ...

Abstract	Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule comparable to PD-1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. LAG-3 is the third inhibitory receptor to be exploited in human anti-cancer immunotherapies, and it is considered a potential next-generation cancer immunotherapy target in human therapy, right next to PD-1 and CTLA-4. Unlike PD-1 and CTLA-4, the exact mechanisms of action of LAG-3 and its relationship with other immune checkpoint molecules remain poorly understood. This is partly caused by the presence of non-conventional signaling motifs in its intracellular domain that are different from other conventional immunoregulatory signaling motifs but with similar inhibitory activities. Here we summarize the current understanding of LAG-3 signaling and its role in LAG-3 functions, from its mechanisms of action to clinical applications.
MeSH term(s)	Antigens, CD/metabolism ; Antigens, CD/physiology ; Humans ; Immunotherapy ; Lymphocyte Activation ; Neoplasms/metabolism ; Receptors, Immunologic/metabolism ; Signal Transduction/physiology ; T-Lymphocytes/immunology
Chemical Substances	Antigens, CD ; CD223 antigen ; Receptors, Immunologic
Language	English
Publishing date	2021-05-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22105282
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