Immunology and Biotherapies
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Science Translational Medicine | From AAAS

Preventing thrombosis without increasing bleeding risk: new antibody blocks Factor XIIa. http://t.co/COiK8Jns9W #surgery
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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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Press Release: Biosimilars & Reference Biologics

Official statement from ACR applauding the FDA for guidance requiring distinct suffixes for biosimilars and reference biologics.
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Pulse Therapy & Lupus Nephritis: A 40-Year History, 1976–2016 - The Rheumatologist

Pulse Therapy & Lupus Nephritis: A 40-Year History, 1976–2016 - The Rheumatologist | Immunology and Biotherapies | Scoop.it
Corticosteroids still represent the mainstay of treatment of patients with active disease. They have been used for more than 60 years, and although prolonged use is associated with organ damage, they have been shown to be lifesaving in various phases of the history of the disease. You Might Also Like 2014 ACR/ARHP Annual Meeting: Lupus... [Read More]
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Radiotherapy and immunotherapy: a beneficial liaison? : Nature Reviews Clinical Oncology : Nature Research

Radiotherapy and immunotherapy: a beneficial liaison? : Nature Reviews Clinical Oncology : Nature Research | Immunology and Biotherapies | Scoop.it
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B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy

B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy | Immunology and Biotherapies | Scoop.it
Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels. Responders to desensitization had a decrease of 5% points or greater in cumulated calculated panel reactive antibody (cPRA) levels, and non-responders had no decrease in cPRA. Dominant B cell clones were not observed in highly sensitized candidates, suggesting that the B cells responsible for sensitization are either not present in peripheral blood or present at comparable levels to other circulating B cells. Candidates that responded to desensitization therapy had pre-treatment repertoires composed of a larger fraction of class-switched (IgG and IgA) isotypes compared to non-responding candidates. After B cell depleting therapy, the proportion of switched isotypes increased and the mutation frequencies of the remaining non-switched isotypes (IgM and IgD) increased in both responders and non-responders, perhaps representing a shift in the repertoire towards memory B cells or plasmablasts. Conversely, after transplantation, non-switched isotypes with fewer mutations increased, suggesting a shift in the repertoire towards naïve B cells. Relative abundance of different B cell isotypes is strongly perturbed by desensitization therapy and transplantation, potentially reflecting changes in the relative abundance of memory and naïve B cell compartments. Candidates that responded to therapy experienced similar changes to those that did not respond. Further studies are required to understand differences between these two groups of highly sensitized kidney transplant candidates.
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Intravenous Immunoglobulin: Overview, Uses of Intravenous Immunoglobulin, Pharmacology and Monitoring

Intravenous Immunoglobulin: Overview, Uses of Intravenous Immunoglobulin, Pharmacology and Monitoring | Immunology and Biotherapies | Scoop.it
Immune globulin products from human plasma were first used in 1952 to treat immune deficiency. Intravenous immunoglobulin (IVIG) contains the pooled immunoglobulin G (IgG) immunoglobulins from the plasma of approximately a thousand or more blood donors.
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TGF-Beta Targeted by New Antibody-Based Therapy

TGF-beta may be an “old story” in the study of cancer but a plot twist was recently encountered by scientists from the Medical University of So
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New anti-IL-23 drugs raise hopes for psoriasis plaque clearance

Nature Biotechnology | doi:10.1038/nbt1216-1218
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CRISPR gene editing takes on rare immunodeficiency disorder

CRISPR gene editing takes on rare immunodeficiency disorder | Immunology and Biotherapies | Scoop.it
Researchers have harnessed the CRISPR-Cas9 technology to correct mutations in the blood stem cells of patients with a rare immunodeficiency disorder; the engineered cells successfully engrafted in mice for up to five months.
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Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining Treg and antitumor CTL function

Targeting Aurora kinase A and JAK2 prevents GVHD while maintaining Treg and antitumor CTL function | Immunology and Biotherapies | Scoop.it
Donor T cell–mediated graft-versus-host disease (GVHD) is a serious complication of stem cell transplantation, but complete inhibition of T cell activation might leave the patient susceptible to leukemia relapse. Betts et al. targeted two kinases involved in T cell costimulation and cytokine-responsiveness to blunt T cell responses. Dual targeting drove human CD4 T cells to become potently suppressive T regulatory cells instead of TH17 effector cells and also prevented GVHD in a humanized mouse model. CD8 T cells were capable of activation after a tumor challenge, indicating that patients receiving this treatment might be able to mount antileukemia responses.
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Cancer spread cut by 75% in tests - BBC News

Cancer spread cut by 75% in tests - BBC News | Immunology and Biotherapies | Scoop.it
Research could lead to new drugs to stop cancer reaching other parts of the body.
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The life cycle of a T cell after vaccination – where does immune ageing strike?

The life cycle of a T cell after vaccination – where does immune ageing strike? | Immunology and Biotherapies | Scoop.it
Vaccination is the optimal intervention to prevent the increased morbidity and mortality from infection in older individuals and to maintain immune health during ageing. To optimize benefits fro
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Prostate Ca: Immunotherapy consensus statement published

Statement authors recommend using immunotherapy prior to an androgen receptor-targeted agent in men with metastatic castration-resistant prostate cancer.
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Cancer immunotherapy [mdash] immune checkpoint blockade and associated endocrinopathies : Nature Reviews Endocrinology : Nature Research

Cancer immunotherapy [mdash] immune checkpoint blockade and associated endocrinopathies : Nature Reviews Endocrinology : Nature Research | Immunology and Biotherapies | Scoop.it
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Cancer Research UK, CRT and MRC to target cancer immunotherapies

Cancer Research UK, CRT and MRC to target cancer immunotherapies | Immunology and Biotherapies | Scoop.it
Cancer Research UK, Cancer Research Technology (CRT) and MRC Technology are set to collaborate in a bid to focus on cancer immunotherapies.
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The First off-the-shelf CAR-T Cancer Therapy gets ready for Clinical Trials

The First off-the-shelf CAR-T Cancer Therapy gets ready for Clinical Trials | Immunology and Biotherapies | Scoop.it
Cellectis is preparing to start the first clinical trial ever using an allogeneic CAR-T therapy that could reduce time and costs over its competitors.
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Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate t... - PubMed - NCBI

Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate t... - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
J Am Acad Dermatol. 2016 Dec 29. pii: S0190-9622(16)31158-6. doi: 10.1016/j.jaad.2016.11.042. [Epub ahead of print]
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Researchers Develop New Method for Silencing Specific Genes in Human T-Cells | Genetics | Sci-News.com

Researchers Develop New Method for Silencing Specific Genes in Human T-Cells | Genetics | Sci-News.com | Immunology and Biotherapies | Scoop.it
An international team of researchers led by Nanyang Technological University, Singapore, has developed a novel technique for gene silencing in human T-lymphocytes (T-cells), a type of immune cells.
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Antibodies to watch in 2017

Antibodies to watch in 2017 | Immunology and Biotherapies | Scoop.it

Antibodies to watch in 2017. mAbs. Accepted 5 December 2016. doi: 10.1080/19420862.2016.1269580


Abstract Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6–9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US. Brodalumab, was granted a first approval in Japan in July 2016. Regulatory actions on marketing applications for brodalumab in the EU and US are not expected until 2017; however, a regulatory action on the biologics license application for ocrelizumab is expected by the end of 2016. In 2017, first EU or US approvals may be granted for at least eight other mAbs (avelumab, Xilonix, inotuzumab ozogamicin, dupilumab, sirukumab, sarilumab, guselkumab, romosozumab) that are not yet approved in any country. Based on announcements of company plans for regulatory submissions and the estimated completion dates for late-stage clinical studies, and assuming the study results are positive, marketing applications for at least 6 antibody therapeutics (benralizumab, tildrakizumab, emicizumab, galcanezumab, ibalizumab, PRO-140) that are now being evaluated in late-stage clinical studies may be submitted during December 2016 or 2017. Other ‘antibodies to watch’ in 2017 include 20 mAbs are undergoing evaluation in pivotal studies that have estimated primary completion dates in late 2016 or during 2017. Of these, 5 mAbs are for cancer (durvalumab, JNJ-56022473, ublituximab, anetumab ravtansine, glembatumumab vedotin) and 15 mAbs are for non-cancer indications (caplacizumab, lanadelumab, roledumab, tralokinumab, risankizumab, SA237, emapalumab, suptavumab, erenumab, eptinezumab, fremanezumab, fasinumab, tanezumab, lampalizumab, brolucizumab). Positive results from these studies may enable submission of marketing applications in 2017 or 2018, or provide justification for additional studies. 


 Keywords: antibody therapeutics, Food and Drug Administration, European Medicines Agency, cancer, immune-mediated disorders


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Antibodies to watch in 2017 Janice M. Reichert MAbs Vol. 0 , Iss. Ja,0
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Leukemia - A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

Leukemia - A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo | Immunology and Biotherapies | Scoop.it
Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
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Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immuno... - PubMed - NCBI

Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immuno... - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
Biol Blood Marrow Transplant. 2017 Jan 6. pii: S1083-8791(16)31176-4. doi: 10.1016/j.bbmt.2016.12.619. [Epub ahead of print] Review
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Disease-modifying effect of intravenous immunoglobulin in an experimental model of epilepsy

Disease-modifying effect of intravenous immunoglobulin in an experimental model of epilepsy | Immunology and Biotherapies | Scoop.it
Novel therapies that prevent or modify the development of epilepsy following an initiating brain insult could significantly reduce the burden of this disease.
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Cell Research - Regulatory T cells in cancer immunotherapy

Cell Research - Regulatory T cells in cancer immunotherapy | Immunology and Biotherapies | Scoop.it

Cell Research (2017) 27:109–118. doi:10.1038/cr.2016.151; published online 20 December 2016 Regulatory T cells in cancer immunotherapy Atsushi Tanaka1,2 and Shimon Sakaguchi1 


Abstract FOXP3-expressing regulatory T (Treg) cells, which suppress aberrant immune response against self-antigens, also suppress anti-tumor immune response. Infiltration of a large number of Treg cells into tumor tissues is often associated with poor prognosis. There is accumulating evidence that the removal of Treg cells is able to evoke and enhance anti-tumor immune response. However, systemic depletion of Treg cells may concurrently elicit deleterious autoimmunity. One strategy for evoking effective tumor immunity without autoimmunity is to specifically target terminally differentiated effector Treg cells rather than all FOXP3+ T cells, because effector Treg cells are the predominant cell type in tumor tissues. Various cell surface molecules, including chemokine receptors such as CCR4, that are specifically expressed by effector Treg cells can be the candidates for depleting effector Treg cells by specific cell-depleting monoclonal antibodies. In addition, other immunological characteristics of effector Treg cells, such as their high expression of CTLA-4, active proliferation, and apoptosis-prone tendency, can be exploited to control specifically their functions. For example, anti-CTLA-4 antibody may kill effector Treg cells or attenuate their suppressive activity. It is hoped that combination of Treg-cell targeting (e.g., by reducing Treg cells or attenuating their suppressive activity in tumor tissues) with the activation of tumor-specific effector T cells (e.g., by cancer vaccine or immune checkpoint blockade) will make the current cancer immunotherapy more effective. 


 Keywords: Treg; CTLA-4; cancer; immunotherapy


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Therapeutic monoclonal antibodies and derivatives: Historical perspectives and future directions

Therapeutic monoclonal antibodies and derivatives: Historical perspectives and future directions | Immunology and Biotherapies | Scoop.it

Abstract Biologics, both monoclonal antibodies (mAbs) and fusion proteins, have revolutionized the practice of medicine. This year marks the 30th anniversary of the Food and Drug Administration approval of the first mAb for human use. In this review, we examine the biotechnological breakthroughs that spurred the explosive development of the biopharmaceutical mAb industry, as well as how critical lessons learned about human immunology informed the development of improved biologics. We also discuss the most common mechanisms of action of currently approved biologics and the indications for which they have been approved to date.


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30 years already...
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Krishan Maggon 's curator insight, January 10, 8:53 AM
Biotechnology Advances Volume 34, Issue 6, 1 November 2016, Pages 1149–1158
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Monoclonal Antibodies against Epidermal Growth Factor Receptor Acquire an Ability To Kill Tumor Cells through Complement Activation by Mutations That Selectively Facilitate the Hexamerization of Ig...

Triggering of the complement cascade induces tumor cell lysis via complement-dependent cytotoxicity (CDC) and attracts and activates cytotoxic cells. It therefore represents an attractive mechanism for mAb in cancer immunotherapy development. The classical complement pathway is initiated by IgG molecules that have assembled into ordered hexamers after binding their Ag on the tumor cell surface. The requirements for CDC are further impacted by factors such as Ab epitope, valency, and affinity. Thus, mAb against well-validated solid tumor targets, such as the epidermal growth factor receptor (EGFR) that effectively induces complement activation and CDC, are highly sought after. The potency of complement activation by IgG Abs can be increased via several strategies. We identified single-point mutations in the Fc domain (e.g., E345K or E430G) enhancing Fc:Fc interactions, hexamer formation, and CDC after Ab binds cell-surface Ag. We show that EGFR Abs directed against clinically relevant epitopes can be converted into mAb with unprecedented CDC activity. Alternative strategies rely on increasing the affinity of monomeric IgG for C1q by introduction of a quadruple mutation at the C1q binding site or via generation of an IgG1/IgG3 chimera. In this study we show that selective enhancement of C1q binding via avidity modulation is superior to the unattended increase in C1q binding via affinity approaches, particularly for target cells with reduced EGFR expression levels. Improving Fc:Fc interactions of Ag-bound IgG therefore represents a highly promising and novel approach for potentiating the anti-tumor activity of therapeutic mAb against EGFR and potentially other tumor targets.
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Clinical and immunologic impact of CCR5 blockade in graft-versus-host disease prophylaxis. - PubMed - NCBI

Clinical and immunologic impact of CCR5 blockade in graft-versus-host disease prophylaxis. - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
Blood. 2017 Jan 5. pii: blood-2016-08-735076. doi: 10.1182/blood-2016-08-735076. [Epub ahead of print]
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