Immunology and Biotherapies
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Targeting the IL-6/JAK/STAT3 signalling axis in cancer

Targeting the IL-6/JAK/STAT3 signalling axis in cancer | Immunology and Biotherapies | Scoop.it

Review


The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response. Thus, treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity. Agents targeting IL-6, the IL-6 receptor, or JAKs have already received FDA approval for the treatment of inflammatory conditions or myeloproliferative neoplasms and for the management of certain adverse effects of chimeric antigen receptor T cells, and are being further evaluated in patients with haematopoietic malignancies and in those with solid tumours. Novel inhibitors of the IL-6/JAK/STAT3 pathway, including STAT3-selective inhibitors, are currently in development. Herein, we review the role of IL-6/JAK/STAT3 signalling in the tumour microenvironment and the status of preclinical and clinical investigations of agents targeting this pathway. We also discuss the potential of combining IL-6/JAK/STAT3 inhibitors with currently approved therapeutic agents directed against immune-checkpoint inhibitors.


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Immunology and Biotherapies
Page Ressources et Actualités du DIU immunologie et biothérapies
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Resources for DIU Immunologie et Biothérapies

DIU Immunologie et Biotherapies is a french diploma associating many french universities and immunology laboratories. It is dedicated to the involvement of immunology in new biotherapies, either molecular or cellular

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We choose Scoop.it as preferred curation tool to collect, select, comment informations flowing on the web in this rapidly evolving theme to keep teachers abreast of scientific knowledge and help students surf the wave...

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in Immunology also use http://www.scoop.it/t/immunology

in Mucosal Immunity http://www.scoop.it/t/mucosal-immunity

in Flow Cytometry and Cytomics http://www.scoop.it/t/from-flow-cytometry-to-cytomics

in Allergy an Clinical Immunology http://www.scoop.it/t/allergy-and-clinical-immunology

in Autoimmunity http://www.scoop.it/t/autoimmunity

 

For further informantions on Immune monitoring of Immune therapies, go to

http://www.scoop.it/t/immune-monitoring-1

by MdC

 

Looking for cancer applications inside this topic, use

http://www.scoop.it/t/immunology-and-biotherapies?q=cancer

 

Looking for cytokines and chemokines, use

http://www.scoop.it/t/cytokines-et-chimiokines

 

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Adipose stem cells enhance excisional wound healing in a porcine model

Adipose stem cells enhance excisional wound healing in a porcine model | Immunology and Biotherapies | Scoop.it
Adipose-derived stem cells (ASCs) are capable of secreting regenerative growth factors
and replacing multiple tissue types. Although current literature suggests that ASCs accelerate wound healing and reduce scarring, the dose-response relationship has not been adequately investigated in large...
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A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi

A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi | Immunology and Biotherapies | Scoop.it
The first series of patients transplanted with autologous marrow for lymphomas was
reported in 1978, using the BACT (carmustine [bis-chloroethylnitrosourea (BCNU)]-cytarabine-cyclophosphamide-thioguanine)
regimen [1].
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Rescooped by Gilbert C FAURE from Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
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Regulatory T cells in the treatment of disease

Regulatory T cells in the treatment of disease | Immunology and Biotherapies | Scoop.it
Abstract
Regulatory T (Treg) cells suppress inflammation and regulate immune system activity. In patients with systemic or organ-specific autoimmune diseases or those receiving transplanted organs, Treg cells are compromised. Approaches to strengthen Treg cell function, either by expanding them ex vivo and reinfusing them or by increasing the number or capacity of existing Treg cells, have entered clinical trials. Unlike the situation in autoimmunity, in patients with cancer, Treg cells limit the antitumour immune response and promote angiogenesis and tumour growth. Their immunosuppressive function may, in part, explain the failure of many immunotherapies in cancer. Strategies to reduce the function and/or number of Treg cells specifically in tumour sites are being investigated to promote antitumour immunity and regression. Here, we describe the current progress in modulating Treg cells in autoimmune disorders, transplantation and cancer.

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FDA approves first drug designed to prevent chronic migraines

FDA approves first drug designed to prevent chronic migraines | Immunology and Biotherapies | Scoop.it
The drug, Aimovig, is a monthly injection with a device similar to an insulin pen
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Putting Natural Killer Cells to the Test in Cancer Immunotherapy

Putting Natural Killer Cells to the Test in Cancer Immunotherapy | Immunology and Biotherapies | Scoop.it
NK cells are “first responders” that rapidly detect and attack virus-infected cells and tumor cells, and can also help prevent metastasis.
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Cell Therapies in Tendon, Ligament, and Musculoskeletal System Repair. - PubMed - NCBI

Cell Therapies in Tendon, Ligament, and Musculoskeletal System Repair. - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
Sports Med Arthrosc Rev. 2018 Jun;26(2):48-58. doi: 10.1097/JSA.0000000000000192.Review...
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Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration | Immunology and Biotherapies | Scoop.it
Immunogenicity of AAV vectors renders repeated AAV dosing ineffective. Here the authors show that coadministration of nanoparticle-encapsulated rapamycin overcomes AAV immunogenicity through Treg induction, enabling efficient AAV redosing in mice and nonhuman primates.
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JCI Insight - Enhanced detection of neoantigen-reactive T cells targeting unique and shared oncogenes for personalized cancer immunotherapy

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Partially Open HIV-1 Envelope Structures Exhibit Conformational Changes Relevant for Coreceptor Binding and Fusion

Partially Open HIV-1 Envelope Structures Exhibit Conformational Changes Relevant for Coreceptor Binding and Fusion | Immunology and Biotherapies | Scoop.it
HIV-1 Env undergoes conformational changes after binding to host receptor CD4 that
allow coreceptor binding, resulting in fusion between host and viral membranes. Wang,
Barnes et al. solved cryo-EM structures of CD4-bound Envs, revealing the order of changes involved in coreceptor binding-site...
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Frontiers | Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen | Immunology

Frontiers | Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen | Immunology | Immunology and Biotherapies | Scoop.it
There is a need for new vaccine adjuvant strategies that offer both vigorous antibody and T-cell mediated protection to combat difficult intracellular pathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 or coagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previous results demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellular responses without toxic systemic effects. These responses were superior to those induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In this study, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicit CD8+ T-cell response and some of the underlying cellular and molecular mechanisms involved in adaptive response. We also analyzed whether this adjuvant strategy allows a switch from an immunization scheme of three-doses to one of single-dose. Our results demonstrated that vaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoral response and importantly-high quality CD8+ T-cell immunity with a single-dose immunization. Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells. The CD8+ T-cell response induced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferon
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Invasive breast cancers punch tunnels into neighboring tissue

Invasive breast cancers punch tunnels into neighboring tissue | Immunology and Biotherapies | Scoop.it
Malignant breast cancer cells can extend protrusions known as invadopodia to dig escape tunnels through surrounding tissue.
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VaccinesToday

VaccinesToday | Immunology and Biotherapies | Scoop.it
We are an online platform for discussing vaccines and vaccination. The platform strives to provide an interactive forum for debate as well as serving as a source of reliable information.
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Response to therapeutic monoclonal antibodies for multiple myeloma in African Americans versus whites - Chehab - - Cancer - Wiley Online Library

Background Myeloma occurs disproportionately in African Americans, with disparities in outcomes potentially caused by access to care, cytogenetics, and immunity. A gap in knowledge of immune function dissimilarities between African Americans and whites exists. Data for other diseases suggest innate differences in immunity and inflammatory markers, with potential implications for therapeutic monoclonal antibodies reliant on secondary immune activation for activity. Methods Patients receiving daratumumab or elotuzumab, lenalidomide, and dexamethasone were retrospectively studied with a primary endpoint of response at 2 (daratumumab) or 4 months (elotuzumab). Secondary endpoints included stable disease or better at the same points, treatment duration, time to best response, and adverse events. Results Eighty patients were included; baseline characteristics were balanced with the exception of the stage at diagnosis, which was more advanced in African Americans. No statistically significant difference in response was seen: 37.9% in whites versus 11.8% in African Americans with daratumumab (P = .090) and 60% in whites versus 44% in African Americans with elotuzumab (P = .462). There were no differences in the duration of treatment, the time to best response, or adverse events. Common potential immune‐related adverse events in both arms were fatigue (39%), back pain (30%), and infusion reactions (40%). Anemia was significantly associated with a response to daratumumab (P = .02); no patients without anemia responded at 2 months, whereas 34.4% of patients with anemia did. Conclusions No significant difference in response, duration of treatment, or time to response was seen by race, although a trend toward greater early response rates in whites was observed. In these cohorts, as in other analyses, African American patients tended to present with later stage disease.
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PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells

PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells | Immunology and Biotherapies | Scoop.it
Author Summary Congenital infection by human cytomegalovirus (HCMV) might result in permanent neurological sequelae, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities.
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Concurrent infection with Mycobacterium tuberculosis confers robust protection against secondary infection in macaques

Concurrent infection with Mycobacterium tuberculosis confers robust protection against secondary infection in macaques | Immunology and Biotherapies | Scoop.it
Author summary Tuberculosis (TB), a lung disease caused by the bacterial pathogen Mycobacterium tuberculosis, is endemic in many developing countries. This infection is transmitted from a person with active tuberculosis through coughing, talking, and singing. Exposure to this bacterium can result in a spectrum of infection outcomes, including in the majority of persons asymptomatic infection, known as latent TB. However, re-exposure to those with active disease occurs frequently, particularly in crowded conditions. Here we demonstrate that ongoing Mtb infection in a non-human primate model provides robust protection against reinfection and disease. This has important implications for vaccine development against this infection.
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CAR T-cells for T-cell malignancies: challenges in distinguishing between therapeutic, normal, and neoplastic T-cells

CAR T-cells for T-cell malignancies: challenges in distinguishing between therapeutic, normal, and neoplastic T-cells | Immunology and Biotherapies | Scoop.it
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Mechanisms of molecular resistance and predictors of response to biological therapy in inflammatory bowel disease

Biological therapy has led to marked improvements in treatment of patients with inflammatory
bowel disease, and an increasing number of drugs has been approved for treatment. However, only a subgroup of patients responds to therapy, highlighting the need to identify biomarkers for therapeutic...
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[Academic] Public Knowledge and Perceptions of Monoclonal Antibodies Survey [18+] : datascience

[Academic] Public Knowledge and Perceptions of Monoclonal Antibodies Survey [18+] : datascience | Immunology and Biotherapies | Scoop.it
r/datascience:...
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Science + Science Writing: The Wild West of stem cell therapy | ScienceWriters2018

Science + Science Writing: The Wild West of stem cell therapy | ScienceWriters2018 | Immunology and Biotherapies | Scoop.it
Twenty years ago, in November 1998, human embryonic stem (ES) cells were introduced to the world. Derived in a nondescript laboratory at the University of Wisconsin, the master cells of human development sparked immediate hope for an inexhaustible supply of cells for therapy to potentially treat conditions such as Parkinson’s, diabetes, heart disease, spinal cord injury, and other disorders. ES cells are now widely used in research and for industrial applications such as drug screening. Their use in the clinic has lagged, but as of late 2017 at least 18 clinical trials in six countries have been launched to test the therapeutic efficacy of ES cells. In the meantime, the advent of induced pluripotent stem cells, where skin and other adult cells are genetically reprogrammed to behave like stem cells, coupled with a dearth of regulation, has enabled unproven treatments to come to market, in some cases with tragic consequences. This session will explore the Wild West landscape of stem cell therapy and how to separate legitimate science from snake oil. Social media hashtag: #WildWestStemCells
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Feasibility of desensitizing children highly allergic to peanut by high‐dose oral immunotherapy - Reier‐Nilsen - - Allergy - Wiley Online Library

1 Background There are limited data on the feasibility, efficacy and safety of high‐dose oral immunotherapy (OIT) in children highly allergic to peanuts. 2 Objective In children highly allergic to peanut, we primarily aimed to determine the feasibility of reaching the maximum maintenance dose (MMD) of 5000 mg peanut protein or, alternatively, a lower individual maintenance dose (IMD), by OIT up‐dosing. Secondarily, we aimed to identify adverse events (AEs) and determine factors associated with reaching a maintenance dose. 3 Methods The TAKE‐AWAY peanut OIT trial enrolled 77 children 5‐15 years old, with a positive oral peanut challenge. Fifty‐seven were randomized to OIT with biweekly dose step‐up until reaching MMD or IMD and 20 to observation only. Demographic and biological characteristics, AEs, medication and protocol deviations were explored for associations with reaching maintenance dose. 4 Results All children had anaphylaxis defined by objective symptoms in minimum two organ systems during baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5% discontinued OIT. During up‐dosing, 19.4% experienced anaphylaxis. Not reaching the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and social reasons (6.7%). Increased peanut s‐IgG4/s‐IgE ratio (OR [95% CI]: 1.02 [1.00, 1.04]) was associated with reaching MMD. 5 Conclusion Although 75.5% of children with peanut anaphylaxis reached a maintenance dose of 0.25‐5 g, only 21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of anaphylaxis, limited the feasibility of reaching MMD.
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Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis.

Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis. | Immunology and Biotherapies | Scoop.it
A new interesting article has been published in Am J Hematol. 2018 Oct 8. doi: 10.1002/ajh.25308.and titled: Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: …...
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Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy | NEJM

Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy | NEJM | Immunology and Biotherapies | Scoop.it
Summary
JC virus, the cause of progressive multifocal leukoencephalopathy (PML), and the BK virus are genetically similar and share sequence homology in immunogenic proteins. We treated three immunosuppressed patients with PML with ex vivo–expanded, partially HLA-matched, third-party–produced, cryopreserved BK virus–specific T cells. The immunosuppression in these patients was due to the conditioning regimen for cord-blood transplantation in one patient, a myeloproliferative neoplasm treated with ruxolitinib in another, and acquired immunodeficiency syndrome in the third. After T-cell infusion in two of the patients, alleviation of the clinical signs and imaging features of PML was seen and JC virus in the cerebrospinal fluid (CSF) cleared. The other patient had a reduction in JC viral load and stabilization of symptoms that persisted until her death 8 months after the first infusion. Two of the patients had immune reconstitution syndrome. Donor-derived T cells were detected in the CSF after infusion. (Funded by the M.D. Anderson Cancer Center Moon Shots Program and the National Institutes of Health; ClinicalTrials.gov number, NCT02479698.)
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The Evolution of Antibody Patents - IPWatchdog.com

The Evolution of Antibody Patents - IPWatchdog.com | Immunology and Biotherapies | Scoop.it
As the pharmaceutical industry continues to shift toward biologic-based drugs, including monoclonal antibodies, protecting the underlying technology has been and continues to be a priority for companies.

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Pioneering CJD treatment to be used on British patient

Pioneering CJD treatment to be used on British patient | Immunology and Biotherapies | Scoop.it
Doctors are given legal permission to use the man-made antibody on a person for the first time.
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ScienceDirect: Adoptive T cell therapy

Adoptive T cell therapy

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