Immunology and Biotherapies
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Down-Regulating Humoral Immune Responses: Implications for O... : Transplantation

Down-Regulating Humoral Immune Responses: Implications for O... : Transplantation | Immunology and Biotherapies | Scoop.it
Alloantibody can be a major barrier to successful organ transplantation; however, therapy to control antibody production or to alter its impact on the allograft remains limited.
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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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New progress toward finding best cells for liver therapy

New progress toward finding best cells for liver therapy | Immunology and Biotherapies | Scoop.it
In an important step toward using transplanted cells to treat liver failure, researchers demonstrate successful transplantation of fetal rat liver cells to an injured adult rat liver.
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Advancing chimeric antigen receptor T cell therapy with CRISPR/Cas9

Advancing chimeric antigen receptor T cell therapy with CRISPR/Cas9 | Immunology and Biotherapies | Scoop.it

ABSTRACT 


The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared. The potential of genetic manipulation using CRISPR/Cas9 system to generate universal CAR T cells and potent T cells that are resistant to exhaustion and inhibition is explored. We also address the safety concerns associated with the use of CRISPR/Cas9 gene editing and provide potential solutions and future directions of CRISPR application in the field of CAR T cell immunotherapy. As an integration-free gene insertion method, CRISPR/Cas9 holds great promise as an efficient gene knock-in platform. Given the tremendous progress that has been made in the past few years, we believe that the CRISPR/Cas9 technology holds immense promise for advancing immunotherapy. 


 Keywords CRISPR/Cas9 chimeric antigen receptor T lymphocytes adoptive immunotherapy gene therapy 


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Ren, J. & Zhao, Y. Protein Cell (2017). doi:10.1007/s13238-017-0410-x

First Online: 22 April 2017 
DOI: 10.1007/s13238-017-0410-x
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Oncologists await historic first: a pan-tumor predictive marker, for immunotherapy : Nature Biotechnology

Oncologists await historic first: a pan-tumor predictive marker, for immunotherapy : Nature Biotechnology | Immunology and Biotherapies | Scoop.it

Oncologists await historic first: a pan-tumor predictive marker, for #immunotherapy
https://t.co/j3wc5ALvLT https://t.co/SOE81m7dP4


The first cancer drug approval based on a marker, not a tumor type, appears immi-nent. The FDA has set a June 9 action date to decide whether Merck’s checkpoint inhibi-tor Keytruda (pembrolizumab) can be used with a test for microsatellite instability in previously treated cancer patients.


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Nanobody System Tags, Grabs, Drags Proteins in the Cell | GEN Genetic Engineering & Biotechnology News - Biotech from Bench to Business | GEN

Nanobody System Tags, Grabs, Drags Proteins in the Cell | GEN Genetic Engineering & Biotechnology News - Biotech from Bench to Business | GEN | Immunology and Biotherapies | Scoop.it
Nanobody-based system used to control intracellular protein localization and investigate developmental biology
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Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade

Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade | Immunology and Biotherapies | Scoop.it
The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy.
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Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors | Immunology and Biotherapies | Scoop.it
Anti-CD25 antibodies have displayed only modest therapeutic activity against established
tumors. Arce Vargas et al. demonstrate that existing anti-CD25 antibodies fail to
deplete intra-tumoral Treg cells due to upregulation of FcγRIIb within tumors. Fc-optimized
anti-CD25 mediates effective depletion of tumor-infiltrating Treg cells and synergizes
with PD-1 blockade to promote tumor eradication.
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How Fresh Are Your PBMC? | Astarte Biologics

How Fresh Are Your PBMC? | Astarte Biologics | Immunology and Biotherapies | Scoop.it
How does the timing of isolation and cryopreservation following blood sample collection impact cell viability and functionality? Find out here.
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Human-Based Biological and Biomimetic Autologous Therapies for Musculoskeletal Tissue Regeneration

Publication date: March 2017
Source:Trends in Biotechnology, Volume 35, Issue 3
Author(s): Sabino Padilla, Mikel Sánchez, Gorka Orive, Eduardo Anitua
Repairing and regenerating damaged musculoskeletal tissues is one of the greatest challenges in regenerative medicine. Blood contains the essential ingredients to biologically engineer drug delivery devices that provide spatiotemporal control over the availability of a wide range of autologous agents, including small molecules, cytokines, and growth factors. This opinion article summarizes our current knowledge of blood-derived biological drug delivery therapies. The potential mechanisms that control protein release are discussed, along with the biological rationale and effects of their use in different relevant musculoskeletal tissues, including articular cartilage, bone, tendon, muscle, and nerve tissue injuries. Finally, we finally describe the current challenges facing the field and recent advances that should drive novel solutions for the musculoskeletal system.
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Bone Marrow Transplantation - Sensing danger: toll-like receptors and outcome in allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation - Sensing danger: toll-like receptors and outcome in allogeneic hematopoietic stem cell transplantation | Immunology and Biotherapies | Scoop.it
Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.
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Report on the FDA-AACR Immuno-oncology Drug Development Workshop

Report on the FDA-AACR Immuno-oncology Drug Development Workshop | Immunology and Biotherapies | Scoop.it
The FDA-AACR Immuno-oncology Drug Development Workshop was held in Washington, DC, from October 13 to 14, 2016. This interdisciplinary forum included government, industry, and academic leaders in pharmacology and oncology. The aim of the meeting was to discuss methodologies in nonclinical and clinical research, safety monitoring, efficacy endpoints, and statistical evaluation of cancer immunotherapy products. This summary highlights topics and viewpoints raised by the presenters and discussants and should not be viewed as the conclusions or recommendations of the workshop as a whole. Cancer Immunol Res; 5(4); 282–5. ©2017 AACR .
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Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients

Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients | Immunology and Biotherapies | Scoop.it
Immune-related adverse events (irAE) have been described with immune checkpoint inhibitors (ICI), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte–associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab, or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016. We calculated the incidence and RR of selected all-grade and high-grade gastrointestinal, liver, skin, endocrine, and pulmonary irAEs across the trials using random-effect models. Twenty-one trials were included, totaling 11,454 patients, of whom 6,528 received an ICI (nivolumab, 1,534; pembrolizumab, 1,522; atezolizumab, 751; and ipilimumab, 2,721) and 4,926 had not. Compared with non-ICI arms, ICIs were associated with more all-grade colitis (RR 7.66, P < 0.001), aspartate aminotransferase (AST) elevation (RR 1.80; P = 0.020), rash (RR 2.50; P = 0.001), hypothyroidism (RR 6.81; P < 0.001), and pneumonitis (RR 4.14; P = 0.012). Rates of high-grade colitis (RR 5.85; P < 0.001) and AST elevation (RR 2.79; P = 0.014) were higher in the ICI arms. Ipilimumab was associated with a higher risk of all-grade rash ( P = 0.006) and high-grade colitis ( P = 0.021) compared with PD-1/PD-L1 ICIs. Incidence of fatal irAE was < 1%. This meta-analysis offers substantial evidence that ICIs are associated with a small but significant increase in risk of selected all-grade irAEs and high-grade gastrointestinal and liver toxicities. Although fatal irAEs remain rare, AEs should be recognized promptly as early interventions may alleviate future complications. Cancer Immunol Res; 5(4); 312–8. ©2017 AACR .
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Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus: A Multicenter, Double‐Blind, Randomized, Parallel‐Group Trial

Effects of Hydroxychloroquine in Patients With Cutaneous Lupus Erythematosus: A Multicenter, Double‐Blind, Randomized, Parallel‐Group Trial | Immunology and Biotherapies | Scoop.it
To assess the efficacy and tolerability of hydroxychloroquine (HCQ) in patients with cutaneous lupus erythematosus (CLE), in a phase III clinical trial conducted in Japan.We conducted a double‐blind
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T cell revival correlates with lung cancer response to PD-1 immunotherapy

T cell revival correlates with lung cancer response to PD-1 immunotherapy | Immunology and Biotherapies | Scoop.it
In lung cancer patients who were taking immunotherapy drugs targeting the PD-1 pathway, testing for CD8 T cell activation in their blood partially predicted whether their tumors would shrink. The results are scheduled fo
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Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS). - PubMed - NCBI

Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS). - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
Ann Surg. 2017 Apr 19. doi: 10.1097/SLA.0000000000002268. [Epub ahead of print]
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Abstract 
OBJECTIVE: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study. SUMMARY OF BACKGROUND DATA: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option. METHODS: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. 
RESULTS: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months. 
CONCLUSIONS: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.
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Fighting cancer with immunotherapy: Signaling molecule causes regression of blood vessels

Fighting cancer with immunotherapy: Signaling molecule causes regression of blood vessels | Immunology and Biotherapies | Scoop.it
Immunotherapy with T-cells offers great hope to people suffering from cancer. Some initial successes have already been made in treating blood cancer, but treating solid tumors remains a major challenge. The signaling molecul
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There's Never Been a More Exciting Time to Work in the Biological Sciences

There's Never Been a More Exciting Time to Work in the Biological Sciences | Immunology and Biotherapies | Scoop.it
Merck's vice president of infectious disease discovery and chief scientific officer of MRL Cambridge Exploratory Science Center has been in the business for 25 years.
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Assessing gastroenterologist and patient acceptance of biosimilars in ulcerative colitis and Crohn's disease across Germany

Assessing gastroenterologist and patient acceptance of biosimilars in ulcerative colitis and Crohn's disease across Germany | Immunology and Biotherapies | Scoop.it
Objectives This study examined gastroenterologists’ motivation for prescribing biosimilars, assessed their treatment preferences in relation to prescribing behaviour, and explored patient attitudes to biosimilars. Methods Data were taken from the Adelphi Real World Biosimilars Programme, a real-world, cross-sectional study undertaken in 2015–2016 with German gastroenterologists and patients with ulcerative colitis or Crohn’s disease. Gastroenterologists provided data on their prescribing behaviour and attitudes towards biosimilars, and invited the next eight eligible consecutive consulting patients to complete a detailed questionnaire. For analysis, gastroenterologists were split into ‘Investigative’, ‘Conservative’, and ‘Other’ groups. Results Overall, 25 gastroenterologists and 136 patients participated. Biosimilars accounted for <15% of all biologic therapies and >80% of gastroenterologists would prescribe a bio-originator rather than biosimilar as 1st line therapy if unrestricted. Patients showed some reluctance to accept biosimilars, although of those receiving biosimilars, 79% were satisfied with the current treatment of their condition, and 69% were satisfied with the control of symptoms. Although at least 35% of patients in each analysis group reported no concerns when starting treatment with a bio-originator or biosimilar, 41% of previously biologic-naïve patients prescribed a biosimilar indicated potential side effects and potential long-term problems, and 24% not knowing enough about the drug, as concerns. Conclusion Results demonstrate that there is reluctance from patients to accept biosimilars and the need to further educate patients who are unsure to allow them to be involved in decision making, highlighting the importance of patient and physician communication. There remains a need for further research into non-clinical switching and the long term impact of prescribing biosimilars.
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A derivative of platelet-derived growth factor receptor alpha binds to the trimer of human cytomegalovirus and inhibits entry into fibroblasts and endothelial cells

A derivative of platelet-derived growth factor receptor alpha binds to the trimer of human cytomegalovirus and inhibits entry into fibroblasts and endothelial cells | Immunology and Biotherapies | Scoop.it
Author summary Human cytomegalovirus (HCMV) depends on expression of platelet-derived growth factor receptor alpha (PDGFR-alpha) for infection of fibroblasts whereas this cell surface protein is not required for infection of endothelial cells. Surprisingly, pretreatment of HCMV with a soluble derivative of PDGFR-alpha prevents infection of both cell types, most probably via specific binding to the trimeric gH/gL/pUL74 complex. While adsorption is inhibited in both cell types, an additional penetration block occurs only in fibroblasts. The finding that an essential molecular interaction of HCMV with fibroblasts can be subverted for inhibition of the virus provides an antiviral strategy that may be hard to circumvent by the virus.
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A futile cycle in cell therapy : Nature Biotechnology : Nature Research

Should a cell therapy for heart disease with scant evidence of efficacy continue to be tested in humans?
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Frontiers | CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection | Alloimmunity and Transplantation

Frontiers | CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection | Alloimmunity and Transplantation | Immunology and Biotherapies | Scoop.it
Background: During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage related cellular shifts and their polarization status during rejection. Here, we aimed to define and correlate monocyte-macrophage endomyocardial tissue profiles obtained at rejection and time-points prior to rejection, with corresponding serial blood samples in 25 heart transplant recipients experiencing acute cellular rejection. Additionally, 33 healthy individuals served as control. Material and Methods: Using histology, immunohistochemistry, confocal laser scan microscopy and digital imaging expression of CD14, CD16, CD56, CD68, CD80 and CD163 was explored to define monocyte and macrophage tissue profiles during rejection. Fibrosis was investigated using Sirius Red stainings of rejection, non-rejection and one-year biopsies. Expression of co-stimulatory and migration-related molecules on circulating monocytes, and production potential for pro- and anti-inflammatory cytokines were studied using flowcytometry. Results: At tissue level, striking CD16+ monocyte infiltration was observed during rejection (p<0.001). Significantly more CD68+CD163+ M2 macrophages were documented during rejection compared to barely present CD68+CD80+ M1 macrophages. Rejection was associated with severe fibrosis in 1-year biopsies (p<0.001). Irrespective of rejection status, decreased frequencies of circulating CD16+ monocytes were found in patients compared to healthy individuals. Rejection was reflected by significantly increased CD54 and HLA-DR expression on CD16+ monocytes with retained cytokine production potential. Conclusions: CD16+ monocytes and M2- macrophages hallmark the correlates of heart transplant acute cellular rejection on tissue level, and seem to be associated with fibrosis on the long-term.
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Indicators of responsiveness to immune checkpoint inhibitors

Indicators of responsiveness to immune checkpoint inhibitors | Immunology and Biotherapies | Scoop.it
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Rescooped by Gilbert C FAURE from Viruses and Bioinformatics from Virology.uvic.ca
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Monoclonal Antibody Cures Marburg Infection in Monkeys | NIH: National Institute of Allergy and Infectious Diseases

Monoclonal Antibody Cures Marburg Infection in Monkeys | NIH: National Institute of Allergy and Infectious Diseases | Immunology and Biotherapies | Scoop.it
Scientists funded by the National Institutes of Health have found that an experimental treatment cured 100 percent of guinea pigs and rhesus monkeys in late stages of infection with lethal levels of Marburg and Ravn viruses, relatives of the Ebola virus. Although the Marburg and Ravn viruses are less familiar than Ebola virus, both can resemble Ebola in symptoms and outcomes in people, and both lack preventive and therapeutic countermeasures.

Via Bwana Moses
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Entire CD3ε, δ, and γ humanized mouse to evaluate human CD3–mediated therapeutics

Entire CD3ε, δ, and γ humanized mouse to evaluate human CD3–mediated therapeutics | Immunology and Biotherapies | Scoop.it
T cell–mediated immunotherapy is an attractive strategy for treatment in various disease areas.
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Cancer under attack: scans show cancer cell colours

Cancer under attack: scans show cancer cell colours | Immunology and Biotherapies | Scoop.it
Striking images show the vivid and colourful scans of rare cancer tumours of the central nervous system. Pictures were taken by the Eye of Science studio in Reutlingen, Germany.
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