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PubMed Journals Articles About "GITR Agonism Exploited Combination With Checkpoint Blockade Overcome" RSS

11:18 EDT 21st September 2019 | BioPortfolio

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Showing "GITR agonism exploited combination with checkpoint blockade overcome" PubMed Articles 1–25 of 2,100+

Durvalumab in Combination with Olaparib in Patients with Relapsed Small Cell Lung Cancer: Results from a Phase II Study.

Despite high tumor mutation burden, immune checkpoint blockade has limited efficacy in small cell lung cancer (SCLC). We hypothesized that poly (ADP-ribose) polymerase (PARP) inhibition could render SCLC more susceptible to immune checkpoint blockade.


Serological Markers Associated With Response to Immune Checkpoint Blockade in Metastatic Gastrointestinal Tract Cancer.

There are a limited number of predictive biomarkers for hyperprogressive disease (HPD), which is induced by immune checkpoint blockade (ICB) therapy.

Triple threat to cancer: rationale for combining oncolytic viruses, MEK inhibitors, and immune checkpoint blockade.

In a recent edition of , we identified an enhanced therapeutic activity when talimogene laherparepvec (T-VEC) was combined with MEK inhibition in murine melanoma tumor models. MEK inhibition increased viral replication independent of mutation status. Combination therapy increased PD-1/PD-L1 expression and PD-1 blockade further enhanced tumor regression. Further clinical development of this strategy for treating melanomas warranted.


Identification of Chicken GITR and GITR Ligand, Proof of Their Mutual Interaction, and Analysis of Chicken GITR Tissue Distribution by a Novel Antibody That Reveals Expression on Activated T Cells and Erythrocytes.

Glucocorticoid-induced TNFR (GITR) and its ligand, GITRL, belong to the costimulatory members of the TNF superfamily and are crucially involved in the formation and modulation of an effective immune response, comprising innate as well as adaptive mechanisms. In this study, we identify and describe chicken GITR and GITRL, and provide an initial characterization of the newly developed chGITR-specific mAb 9C5. Structural analyses of the putative chicken molecules GITR and GITRL confirmed the conservation of cl...

Combination PD-1 and PD-L1 Blockade Promotes Durable Neoantigen-Specific T Cell-Mediated Immunity in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer resistant to immunotherapy. We create a PDA mouse model and show that neoantigen expression is required for intratumoral T cell accumulation and response to immune checkpoint blockade. By generating a peptide:MHC tetramer, we identify that PDA induces rapid intratumoral, and progressive systemic, tumor-specific T cell exhaustion. Monotherapy PD-1 or PD-L1 blockade enhances systemic T cell expansion and induces objective responses that require syst...

Recent advances in the clinical development of immune checkpoint blockade therapy.

The discovery of immune checkpoint proteins and the mechanisms by which cancer cells utilize them to evade the immune system has transformed our approach to cancer immunotherapy. Checkpoint blockade antibodies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligands such as programmed cell death ligand 1 (PD-L1) have already revolutionized the treatment of multiple types of cancer and have significantly improved treatment and survival outcomes of patients affected ...

Inhibition of QPCTL Induces Myeloid Immune Checkpoint Blockade.

Glutaminyl-peptide cyclotransferase-like (QPCTL) is a modifier of the CD47-SIRPα myeloid checkpoint.

Checkpoint blockade immunotherapy enhances the frequency and effector function of murine tumor-infiltrating T cells but does not alter TCRβ diversity.

Checkpoint blockade immunotherapy is now a first-line treatment option for patients with melanoma. Despite achieving objective responses in about half of patients, the exact immune mechanisms elicited and those required for therapeutic success have not been clearly identified. Insight into these mechanisms is key for improving outcomes in a broader range of cancer patients. We used a murine melanoma model to track responses by different subsets of tumor-infiltrating lymphocytes (TIL) during checkpoint block...

Dual CTLA-4 and PD-L1 Blockade Inhibits Tumor Growth and Liver Metastasis in a Highly Aggressive Orthotopic Mouse Model of Colon Cancer.

Immune checkpoint inhibitors have shown clinical benefit in several cancer entities including metastatic microsatellite instable colorectal carcinomas. However, for the majority of metastatic colorectal carcinomas the potential and limitations of immune checkpoint inhibition is not fully understood. In this study, the effects of sole and dual CTLA-4 and PD-L1 blockade were investigated in a microsatellite stable highly aggressive orthotopic mouse model of colon cancer. Dual CTLA-4 and PD-L1 inhibition resul...

Immune checkpoint blockade in small cell lung cancer.

Despite the highly immunogenic potential of small cell lung cancer (SCLC), progress in evaluating the therapeutic value of immune checkpoint agents has lagged behind that of non-small cell lung cancer. Results from a number of phase I-III clinical trials that specifically address the use of anti-PD-1, anti-PD-L1 and anti-CTLA-4 agents in SCLC have now been reported. This review will focus on the available evidence for immune checkpoint blockade in SCLC and review current biomarker strategies with the aim of...

Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer.

Immune checkpoint blockade with PD-1/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockad...

SnapShot: Cancer Immunotherapy with Oncolytic Viruses.

Oncolytic viruses (OVs) preferentially infect and kill cancer cells without harming normal cells. OVs can revert cancer-associated immune suppression and initiate clinically meaningful antitumor immune responses. OVs and their resultant immunological events can act at both primary and metastatic sites. Thus, OVs can be exploited for cancer gene therapies and immunotherapies alone or in combination with other interventions, including immune checkpoint blockade.

Chimeric antigen receptor T cell therapy and other therapeutics for malignancies: Combination and opportunity.

Chimeric antigen receptor T (CAR-T) cell therapy provides possibility for the treatment of malignancies since clinical trials have shown that CAR-T therapy has a significant anti-tumor effect. Although many efforts have been made to improve the efficacy and reduce the side effects of CAR-T therapy, there are still many problems to solve. With the rapid development of this field, combination immunotherapy has been proved to improve the efficacy of CAR-T therapy. Studies have shown that radiotherapy, chemothe...

High Affinity of Chlorin e6 to Immunoglobulin G for Intraoperative Fluorescence Image-Guided Cancer Photodynamic and Checkpoint Blockade Therapy.

Cancer photodynamic therapy (PDT) represents an attractive local treatment in combination with immunotherapy. Successful cancer PDT relies on the image-guidance to ensure the treatment accuracy. However, existing nanotechnology for co-delivery of photosensitizers and image contrast agents slows the clearance of PDT agents from the body, and causes a disparity between the release profiles of the imaging and PDT agents. We have found that the photosensitizer Chlorin e6 (Ce6) is inherently bound to immunoglobu...

Immune-related pancreatitis associated with checkpoint blockade in melanoma.

Recognizing and treating rare checkpoint inhibitor related adverse events may be a clinical challenge in melanoma therapy. One of rather rare affected organs is the pancreas. Immune-related pancreatitis is difficult to recognize due to its variable clinical characteristics. Asymptomatic elevations of serum lipase and/or amylase during therapy with immune-checkpoint blockade impede the diagnostic process. We present a patient who developed an immune-related pancreatitis within the first 4 months of immunothe...

Large-scale analysis reveals the specific clinical and immune features of CD155 in glioma.

Recent studies demonstrated that CD155 plays an important role in anti-tumor immune responses. However, its role in glioma remains unclear. Here, we identify CD155 as a promising immune target in glioma. CD155 expression was significantly highly expressed in glioblastoma but not in normal brain tissue. Subsequent analysis based on genetic and clinical data from 1173 glioma patients in Rembrandt and TCGA dataset suggested that CD155 related genes of immune response were mainly positively correlated with CD15...

A Dual-Bioresponsive Drug-Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade.

Patients with advanced melanoma that is of low tumor-associated antigen (TAA) expression often respond poorly to PD-1/PD-L1 blockade therapy. Epigenetic modulators, such as hypomethylation agents (HMAs), can enhance the antitumor immune response by inducing TAA expression. Here, a dual bioresponsive gel depot that can respond to the acidic pH and reactive oxygen species (ROS) within the tumor microenvironment (TME) for codelivery of anti-PD1 antibody (aPD1) and Zebularine (Zeb), an HMA, is engineered. aPD1 ...

Immune Checkpoint Blockade plus Axitinib for Renal-Cell Carcinoma.

Novel Dimethyltyrosine-Tetrahydroisoquinoline Peptidomimetics with Aromatic Tetrahydroisoquinoline Substitutions Show In Vitro Kappa and Mu Opioid Receptor Agonism.

The dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold was originally developed in the production of selective delta opioid receptor (DOR) antagonists. Installation of a 7-benzyl pendant on the tetrahydroisoquinoline core of this classic opioid scaffold introduced kappa opioid receptor (KOR) agonism. Further modification of this pendant resulted in retention of KOR agonism and the addition of mu opioid receptor (MOR) partial agonism, a bifunctional profile with potential to be used in the treatment ...

Immune Checkpoint Blockade plus Axitinib for Renal-Cell Carcinoma. Reply.

Immune Checkpoint Blockade plus Axitinib for Renal-Cell Carcinoma. Reply.

PD-L1 expression, tumor mutational burden and cancer gene mutations are stronger predictors of benefit from immune checkpoint blockade than HLA class I genotype in non-small cell lung cancer.

Immune checkpoint blockade (ICB) has revolutionized the treatment of non-small cell lung cancer (NSCLC), but only ∼15% of patients achieve durable benefit. Understanding resistance mechanisms to ICB is pivotal in developing more effective treatment strategies. Recent studies showed human leukocyte antigen (HLA) class I heterozygosity might be important in mediating benefit from ICB. We aimed to investigate the impact of HLA class I genotype on outcomes of NSCLC patients treated with ICB.

Targeting the tumour immune microenvironment for cancer therapy in human gastrointestinal malignancies.

Gastrointestinal (GI) cancer is a malignancy of the GI tract and accessory digestive organs. GI cancer patients develop resistance to chemotherapy, targeted therapy drugs and immune therapies. Although immune checkpoint inhibitors have shown promising clinical results in melanoma, etc., immune checkpoint blockade responds in only a subset of colorectal cancer (CRC) patients with microsatellite instability-high (MSI-H) tumours. The tumour immune microenvironment (TIME) has a dynamic nature during malignant p...

Efficacy of immune checkpoint blockade in MUTYH-associated hereditary colorectal cancer.

Colorectal carcinomas (CRCs) caused by hereditary biallelic MUTYH gene mutations are characterized by elevated mutation load and high lymphocyte infiltration. Given that these tumor features are associated with the response to immune checkpoint inhibitors, we administered nivolumab to a CRC patient who carried two inactive MUTYH alleles (p.Y179C and p.G396D) and previously experienced failure of chemotherapy. This experimental treatment resulted in a pronounced tumor response. We further compared tumor lymp...

Peripheral PD-1+CD56+ T-cell frequencies correlate with outcome in stage IV melanoma under PD-1 blockade.

Immune checkpoint blockade with anti-PD-1 antibodies is showing great promise for patients with metastatic melanoma and other malignancies, but despite good responses by some patients who achieve partial or complete regression, many others still do not respond. Here, we sought peripheral blood T-cell biomarker candidates predicting treatment outcome in 75 stage IV melanoma patients treated with anti-PD-1 antibodies. We investigated associations with clinical response, progression-free survival (PFS) and ove...


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