Immunology and Biotherapies
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Immunology and Biotherapies
Page Ressources et Actualités du DIU immunologie et biothérapies
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Rescooped by Gilbert C FAURE from Cancer Immunotherapy Review
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FDA Approves Keytruda for Head and Neck Cancer

FDA Approves Keytruda for Head and Neck Cancer | Immunology and Biotherapies | Scoop.it
An accelerated FDA approval has been granted to the immunotherapy Keytruda for patients with recurrent or metastatic head and neck squamous cell carcinoma following progression on a platinum-containing chemotherapy.

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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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Rescooped by Gilbert C FAURE from Melanoma BRAF Inhibitors Review
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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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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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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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From Vision to Reality: Deploying the Immune System for Treatment of Sarcoma - Breelyn A Wilky - Discovery Medicine

From Vision to Reality: Deploying the Immune System for Treatment of Sarcoma - Breelyn A Wilky - Discovery Medicine | Immunology and Biotherapies | Scoop.it
Modern immunotherapy advances including checkpoint inhibitors and adoptive T cell therapy have created a new era of cancer treatment, with significant activities in a wide variety of hematologic and solid cancers. Sarcomas are rare and aggressive malignancies of bone and .
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Keystone Symposia - Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology

The fields of cancer immunology and immunotherapy continue to make great strides in providing both a comprehensive understanding of th
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US FDA lifts hold on Seattle Genetics' blood cancer ADC candidate

US FDA lifts hold on Seattle Genetics' blood cancer ADC candidate | Immunology and Biotherapies | Scoop.it
The US FDA has cleared Seattle Genetics to restart trials of its blood cancer candidate vadastuximab talirine that were halted last year after patient deaths. 
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Immunotherapy-associated autoimmune hemolytic anemia. - PubMed - NCBI

Immunotherapy-associated autoimmune hemolytic anemia. - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
J Immunother Cancer. 2017 Feb 21;5:15. doi: 10.1186/s40425-017-0214-9. eCollection 2017.
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Frontiers | Dual Role of Natural Killer Cells on Graft Rejection and Control of Cytomegalovirus Infection in Renal Transplantation | NK and Innate Lymphoid Cell Biology

Frontiers | Dual Role of Natural Killer Cells on Graft Rejection and Control of Cytomegalovirus Infection in Renal Transplantation | NK and Innate Lymphoid Cell Biology | Immunology and Biotherapies | Scoop.it
Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, NK cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIR) and graft HLA class I molecules. Several studies have addressed the impact of this variable in kidney transplant with conflicting conclusions; yet, increasing evidence supports that alloantibody-mediated NK cell activation via FcγRIIIA (CD16) contributes to rejection. On the other hand, human cytomegalovirus (HCMV) infection constitutes a risk factor directly associated to the rate of graft loss and reduced host survival. The levels of HCMV-specific CD8+ T cells have been reported to predict the risk of post-transplant infection, and KIR-B haplotypes containing activating KIR genes have been related with protection. HCMV infection promotes to a variable extent an adaptive differentiation and expansion of a subset of mature NK cells which display the CD94/NKG2C activating receptor. Evidence supporting that adaptive NKG2C+ NK cells may contribute to control the viral infection in kidney transplant recipients (KTR) has been recently obtained. The dual role of NK cells in the interrelation of HCMV infection with rejection deserves attention. Further phenotypic, functional and genetic analyses of NK cells may provide additional insights on the pathogenesis of solid organ transplant complications, leading to the development of biomarkers with potential clinical value.
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Rescooped by Gilbert C FAURE from Top Selling Monoclonal Antibodies 2014
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All Antigens Are Not Created Equal | GEN Genetic Engineering & Biotechnology News - Biotech from Bench to Business | GEN

All Antigens Are Not Created Equal | GEN Genetic Engineering & Biotechnology News - Biotech from Bench to Business | GEN | Immunology and Biotherapies | Scoop.it
Unique tumor mutations called neoantigens could hold the key to personalized cancer therapies.

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Plant-Made Vaccines in the Fight Against Cancer

Trends Immunotherapy is becoming a prominent approach to fight against cancer using treatments of higher efficacy and safety. Plant-based vaccines targeting several types of cancer have been developed over the past two decades. Plant-based vaccines are highly advantageous in terms of costs and safety. Preclinical evaluations have demonstrated potential prophylactic and therapeutic effects using plant-based vaccines. So far, the most prominent development of plant-based vaccines targeting cancer has been personalized vaccines for non-Hodgkin's lymphoma, which are in clinical trials.
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Rescooped by Gilbert C FAURE from Cancer Immunotherapy Review
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The Activating Human NK Cell Receptor KIR2DS2 Recognizes a β2-Microglobulin–Independent Ligand on Cancer Cells

The Activating Human NK Cell Receptor KIR2DS2 Recognizes a β2-Microglobulin–Independent Ligand on Cancer Cells | Immunology and Biotherapies | Scoop.it
The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand–specific immunological synapses. HLA-C typing of target cells showed that KIR2DS2 recognition was independent of the HLA C1 or C2 group, whereas targets cells that were only recognized by KIR2DL3 expressed C1 group alleles. Anti–HLA class I Abs blocked KIR2DL3 responses toward C1-expressing targets, but they did not block KIR2DS2 recognition of cancer cells. Small interfering RNA knockdown of β2-microglobulin reduced the expression of class I H chain on the cancer targets by >97%, but it did not reduce the KIR2DS2 reporter responses, indicating a β2-microglobulin–independent ligand for KIR2DS2. Importantly, KIR2DL3 responses toward some KIR2DS2 ligand–expressing cells were also undiminished after β2-microglobulin knockdown, and they were not blocked by anti–HLA class I Abs, suggesting that KIR2DL3, in addition to the traditional HLA-C ligands, can bind to the same β2-microglobulin–independent ligand as KIR2DS2. These observations indicate the existence of a novel, presently uncharacterized ligand for the activating NK cell receptor KIR2DS2. Molecular identification of this ligand may lead to improved KIR-HLA mismatching in hematopoietic stem cell transplantation therapy for leukemia and new, more specific NK cell–based cancer therapies.

Via Krishan Maggon
Gilbert C FAURE's insight:
interesting new feature of KIR receptor
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A STING-activating nanovaccine for cancer immunotherapy : Nature Nanotechnology : Nature Research

A STING-activating nanovaccine for cancer immunotherapy : Nature Nanotechnology : Nature Research | Immunology and Biotherapies | Scoop.it
STING-activating nanoparticle vaccines achieve robust activation of tumour-specific T cells for cancer immunotherapy.
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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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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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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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Rescooped by Gilbert C FAURE from Top Selling Monoclonal Antibodies 2014
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The Murky Waters of CAR-T Therapy in Cancer Imunotherapy

The Murky Waters of CAR-T Therapy in Cancer Imunotherapy | Immunology and Biotherapies | Scoop.it
New approaches to treating cancer have shown great promise, but they also come with serious risks that give us cause for concern.

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T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition | Immunology and Biotherapies | Scoop.it
Programmed death-1 (PD-1) is a co-inhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). Here, by titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1-recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that co-stimulatory pathways play key roles in regulating effector T cell function and therapeutic responses to anti-PD-L1/PD-1.
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Rescooped by Gilbert C FAURE from Cancer Immunotherapy Review
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Going beyond PD-L1 testing for lung cancer immunotherapy

Going beyond PD-L1 testing for lung cancer immunotherapy | Immunology and Biotherapies | Scoop.it
Jürgen Wolf, MD, University Hospital of Cologne, Cologne, Germany, talks about strategies to select the patients most likely to benefit from immune checkpoint inhibitors, a class of drugs that activate the immune system against tumour cells.

Current selection strategies are based on the expression levels of PD-L1 in the tumour, with higher levels of expression associated with a higher likelihood of response to treatment. However, Prof Wolf points out that PD-L1 expression is not always associated with a good response to immunotherapy. There are cases of PD-L1 positive patients who do not respond to treatment and conversely, cases of PD-L1 negative-patients who benefit from treatment. Therefore, there is a need for better predictive biomarkers to enable more precise treatment decisions. Prof Wolf discusses two strategies for patient selection that go beyond PD-L1 testing.

The first is overall mutational burden, the sum of all mutations present in a tumour cell. The higher the mutation burden, the higher the probability of a response to immunotherapy.

The second strategy aims to look at the tumour micro-environment and the multiple interactions that take place between the different components of the immune system. Transcriptome analysis looks at the activity of the tumour’s whole genome as opposed to gene mutations. By looking at activity of the whole genome, Prof Wolf’s research aims to identify patterns that differentiate patients who will respond to immunotherapy from those who will not. These strategies are currently under investigation and not yet ready to be translated into clinical practice.

Recorded at the 2017 meeting of the British Thoracic Oncology Group (BTOG) in Dublin, Ireland.

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Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody. - PubMed - NCBI

Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody. - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
J Immunother Cancer. 2017 Feb 21;5:20. doi: 10.1186/s40425-017-0220-y. eCollection 2017.
Gilbert C FAURE's insight:
Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers. This study was designed to investigate the effect on immune cell subsets in the peripheral blood of cancer patients prior to and following multiple administrations of avelumab. METHODS: One hundred twenty-three distinct immune cell subsets in the peripheral blood of cancer patients (n = 28) in a phase I trial were analyzed by flow cytometry prior to and following one, three, and nine cycles of avelumab. Changes in soluble (s) CD27 and sCD40L in plasma were also evaluated. In vitro studies were also performed to determine if avelumab would mediate ADCC of PBMC. RESULTS: No statistically significant changes in any of the 123 immune cell subsets analyzed were observed at any dose level, or number of doses, of avelumab. Increases in the ratio of sCD27:sCD40L were observed, suggesting potential immune activation. Controlled in vitro studies also showed lysis of tumor cells by avelumab versus no lysis of PBMC from five donors. CONCLUSIONS: These studies demonstrate the lack of any significant effect on multiple immune cell subsets, even those expressing PD-L1, following multiple cycles of avelumab. These results complement prior studies showing anti-tumor effects of avelumab and comparable levels of adverse events with avelumab versus other anti-PD-1/PD-L1 MAbs. These studies provide the rationale to further exploit the potential ADCC mechanism of action of avelumab as well as other human IgG1 checkpoint inhibitors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01772004 (first received: 1/14/13; start date: January 2013) and NCT00001846 (first received date: 11/3/99; start date: August 1999).
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Rescooped by Gilbert C FAURE from Cancer Immunotherapy Review
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Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies

Cancer immunotherapy — immune checkpoint blockade and associated endocrinopathies | Immunology and Biotherapies | Scoop.it

Nature Reviews Endocrinology | doi:10.1038/nrendo.2016.205


Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T‑lymphocyte antigen4 (CTLA4) and programmed cell deathprotein1 (PD1) are two co‑inhibitory receptors that are expressed on activated Tcells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune‑related adverse events (IRAEs), which resemble autoimmune disease. In this Review, we describe the current data regarding immune-related endocrinopathies, including hypophysitis, thyroid dysfunction and diabetes mellitus. We discuss the clinical management of these endocrinopathies within the context of our current understanding of the mechanisms of IRAEs.


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Krishan Maggon 's curator insight, February 28, 4:32 AM
Nature Reviews Endocrinology | doi:10.1038/nrendo.2016.205
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Efforts Continue to Refine Use of Checkpoint Inhibitors in NSCLC

Efforts Continue to Refine Use of Checkpoint Inhibitors in NSCLC | Immunology and Biotherapies | Scoop.it
Hossein Borghaei, DO, provides additional insight on checkpoint inhibitors, determining patient selection, and how these therapies will continue to significantly impact the treatment landscape in non&ndash;small cell lung cancer for years to come.
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'Final common pathway' of human cancer immunotherapy: targeting random somatic mutations : Nature Immunology : Nature Research

Rosenberg and colleagues review evidence suggesting that T cells that target tumor neoantigens arising from cancer mutations are the main mediators of many effective cancer immunotherapies in humans.
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Guidelines Planned on Management of Immunotherapy Side Effects: ASCO and NCCN to Collaborate on Development

Guidelines Planned on Management of Immunotherapy Side Effects: ASCO and NCCN to Collaborate on Development | Immunology and Biotherapies | Scoop.it
Given the pace of advances in immunotherapy in recent years and physicians’ need to keep up with these developments, the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network® (NCCN®) announce a joint collaboration to publish practical clinical guidance on the management of side effects caused by immunotherapy.
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