1,254 results match your criteria Immunotherapeutic Targeting


CD8 T cell exhaustion.

Authors:
Makoto Kurachi

Semin Immunopathol 2019 Apr 15. Epub 2019 Apr 15.

Department of Molecular Genetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.

CD8 T cells are important for the protective immunity against intracellular pathogens and tumor. In the case of chronic infection or cancer, CD8 T cells are exposed to persistent antigen and/or inflammatory signals. This excessive amount of signals often leads CD8 T cells to gradual deterioration of T cell function, a state called "exhaustion. Read More

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http://dx.doi.org/10.1007/s00281-019-00744-5DOI Listing

Facing the future: challenges and opportunities in adoptive T cell therapy in cancer.

Expert Opin Biol Ther 2019 Apr 15. Epub 2019 Apr 15.

a Department of Oncology-Pathology , Karolinska Institutet , Stockholm , Sweden.

Introduction: In recent years, immunotherapy for the treatment of solid cancer has emerged as a promising therapeutic alternative. Adoptive cell therapy (ACT), especially T cell-based, have been found to cause tumor regression and even cure in a percentage of treated patients. Checkpoint inhibitors further underscore the potential of the T cell compartment in the treatment of cancer. Read More

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https://www.tandfonline.com/doi/full/10.1080/14712598.2019.1
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http://dx.doi.org/10.1080/14712598.2019.1608179DOI Listing
April 2019
3 Reads

Discovery of [1,2,4]Triazolo[4,3- a]pyridines as Potent Inhibitors Targeting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction.

J Med Chem 2019 Apr 19. Epub 2019 Apr 19.

Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University) , Ministry of Education , 103 Wenhua Road , Shenyang 110016 , PR China.

Inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction using small-molecule inhibitors is an emerging immunotherapeutic approach. A novel series of [1,2,4]triazolo[4,3- a]pyridines were designed and found to be potent inhibitors of the PD-1/PD-L1 interaction. Among them, compound A22 exhibited the most potent activity, as assessed by homogenous time-resolved fluorescence assay, with an IC of 92. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.9b00312DOI Listing
April 2019
1 Read
5.447 Impact Factor

Therapeutic approaches for targeting ROR-1 in cancer cells.

Expert Opin Ther Targets 2019 Apr 1. Epub 2019 Apr 1.

d Stem Cell Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.

Introduction: There is a high expression of ROR1, a tyrosine kinase receptor, in various tumor-cell types. ROR1 is involved in many key processes in cancer including proliferation, survival and metastasis. Hence, ROR1 is an attractive and promising therapeutic target. Read More

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http://dx.doi.org/10.1080/14728222.2019.1602608DOI Listing
April 2019
1 Read

TIM-3 in endometrial carcinomas: an immunotherapeutic target expressed by mismatch repair-deficient and intact cancers.

Mod Pathol 2019 Mar 29. Epub 2019 Mar 29.

University of Virginia Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Charlottesville, VA, USA.

The checkpoint molecule TIM-3 is a target for emerging immunotherapies and has been identified on a variety of malignancies. Mismatch repair-deficient endometrial carcinomas have demonstrated durable responses to other checkpoint inhibitors due to high neoantigen loads and robust tumor-associated immune responses. However, little is known about TIM-3 expression in this tumor type. Read More

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http://dx.doi.org/10.1038/s41379-019-0251-7DOI Listing

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma.

Nat Commun 2019 03 29;10(1):1405. Epub 2019 Mar 29.

Division of Immunology, Biomedical Sciences Research Center Alexander Fleming, Vari-Athens, 16672, Greece.

Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic genes. Read More

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http://dx.doi.org/10.1038/s41467-019-09370-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441097PMC

Side effects of immunotherapy: a constant challenge for oncologists.

Curr Opin Oncol 2019 Mar 28. Epub 2019 Mar 28.

Oncology and Supportive Care Department, Hôpital Foch, Suresnes, France.

Purpose Of Review: Immunotherapeutic strategies have become the new paradigm of cancer care, through their new targeting and safety profile approach, and, de facto, their new monitoring and safety management challenges.

Recent Findings: Generalities and specificities of the toxicity management related to immune checkpoint inhibitors (ICIs) are highlighted. Predictive factors of safety are issue of research and the challenge of prevention as well as monitoring are huge to alleviate toxicities and enhance safety and efficacy. Read More

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http://dx.doi.org/10.1097/CCO.0000000000000541DOI Listing

Therapeutic Cancer Vaccine and Combinations With Antiangiogenic Therapies and Immune Checkpoint Blockade.

Front Immunol 2019 14;10:467. Epub 2019 Mar 14.

PARCC (Paris-Cardiovascular Research Center), INSERM U970, Paris, France.

Considering the high importance of immune surveillance and immune escape in the evolution of cancer, the development of immunotherapeutic strategies has become a major field of research in recent decades. The considerable therapeutic breakthrough observed when targeting inhibitory immune checkpoint molecules has highlighted the need to find approaches enabling the induction and proper activation of an immune response against cancer. In this context, therapeutic vaccination, which can induce a specific immune response against tumor antigens, is an important approach to consider. Read More

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http://dx.doi.org/10.3389/fimmu.2019.00467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426771PMC

Immune-enrichment of non-small cell lung cancer baseline biopsies for multiplex profiling define prognostic immune checkpoint combinations for patient stratification.

J Immunother Cancer 2019 Mar 28;7(1):86. Epub 2019 Mar 28.

Institut du cancer de Montréal, Montréal, Québec, Canada.

Background: Permanence of front-line management of lung cancer by immunotherapies requires predictive companion diagnostics identifying immune-checkpoints at baseline, challenged by the size and heterogeneity of biopsy specimens.

Methods: An innovative, tumor heterogeneity reducing, immune-enriched tissue microarray was constructed from baseline biopsies, and multiplex immunofluorescence was used to profile 25 immune-checkpoints and immune-antigens.

Results: Multiple immune-checkpoints were ranked, correlated with antigen presenting and cytotoxic effector lymphocyte activity, and were reduced with advancing disease. Read More

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http://dx.doi.org/10.1186/s40425-019-0544-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437930PMC
March 2019
1 Read

Targeting natural killer cells in solid tumors.

Cell Mol Immunol 2019 May 25;16(5):415-422. Epub 2019 Mar 25.

Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, Marseille, France.

Natural killer (NK) cells are innate lymphoid cells endowed with cytolytic activity and a capacity to secrete cytokines and chemokines. Several lines of evidence suggest that NK cells play an important role in anti-tumor immunity. Some therapies against hematological malignacies make use of the immune properties of NK cells, such as their ability to kill residual leukemic blasts efficiently after conditioning during haploidentical hematopoietic stem cell transplantation. Read More

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http://dx.doi.org/10.1038/s41423-019-0224-2DOI Listing
May 2019
1 Read

Expandable Immunotherapeutic Nanoplatforms Engineered from Cytomembranes of Hybrid Cells Derived from Cancer and Dendritic Cells.

Adv Mater 2019 Mar 25:e1900499. Epub 2019 Mar 25.

Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.

Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co-stimulatory molecules for robust immunotherapy. FMs share the tumor's self-targeting character with the parent cancer cells. Read More

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http://dx.doi.org/10.1002/adma.201900499DOI Listing

Novel immunotherapeutic approaches for hepatocellular carcinoma treatment.

Expert Rev Clin Pharmacol 2019 Mar 23:1-18. Epub 2019 Mar 23.

a Experimental and Clinical Pharmacology Unit , Centro di Riferimento Oncologico di Aviano (CRO), IRCCS , Aviano (PN) , Italy.

Introduction: The introduction of immune checkpoint inhibitors has been lately proposed for the treatment of hepatocellular carcinoma (HCC) with respect to other cancer types. Several immunotherapeutic approaches are now under evaluation for HCC treatment including: i) antibodies acting as immune checkpoint inhibitors; ii) antibodies targeting specific tumor-associated antigens; iii) chimeric antigen receptor redirected T (CAR-T) cells targeting specific tumor-associated antigens; iv) vaccination strategies with tumor-specific epitopes. Areas covered: The review provides a wide description of the clinical trials investigating the efficacy of the main immunotherapeutic approaches proposed for the treatment of patients affected by HCC. Read More

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http://dx.doi.org/10.1080/17512433.2019.1598859DOI Listing

Anti-tumor immunity induced by ectopic expression of viral antigens is transient and limited by immune escape.

Oncoimmunology 2019 6;8(4):e1568809. Epub 2019 Feb 6.

Department of Oral & Maxillofacial Surgery, University of Texas Health Science Center at Houston, School of Dentistry, Houston, TX, USA.

Immunotherapeutic treatments in head and neck cancer clinical trials include cancer vaccines targeting foreign viral antigens or mutational neoantigens derived from cancer-expressed proteins. Anti-tumor immune responses place cancer cells under selective pressure to lose or downregulate target antigens; therefore, vaccination against virus- or host- "driver" oncogenes are proposed as a strategy to overcome immune escape. Herein, we demonstrate the impact of immunogenic viral antigens on anti-tumor response and immune editing in MOC2-E6E7, a syngeneic murine oral cancer cell line expressing HPV-16 E6 and E7 oncoproteins. Read More

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http://dx.doi.org/10.1080/2162402X.2019.1568809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422387PMC
February 2019

Role of natural killer cells for immunotherapy in chronic myeloid leukemia (Review).

Oncol Rep 2019 May 13;41(5):2625-2635. Epub 2019 Mar 13.

Department of Biomedical Science, CHA University, CHA General Hospital, Seongnam, Gyeonggi 13488, Republic of Korea.

The majority of natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy. The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. Read More

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http://dx.doi.org/10.3892/or.2019.7059DOI Listing

Broad Cytotoxic Targeting of Acute Myeloid Leukemia by Polyclonal Delta One T Cells.

Cancer Immunol Res 2019 Apr 20;7(4):552-558. Epub 2019 Mar 20.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

Acute myeloid leukemia (AML) remains a clinical challenge due to frequent chemotherapy resistance and deadly relapses. We are exploring the immunotherapeutic potential of peripheral blood Vδ1 T cells, which associate with improved long-term survival of stem-cell transplant recipients but have not yet been applied as adoptive cell therapy. Using our clinical-grade protocol for expansion and differentiation of "Delta One T" (DOT) cells, we found DOT cells to be highly cytotoxic against AML primary samples and cell lines, including cells selected for resistance to standard chemotherapy. Read More

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http://dx.doi.org/10.1158/2326-6066.CIR-18-0647DOI Listing
April 2019
1 Read

Novel CD19-targeted TriKE restores NK cell function and proliferative capacity in CLL.

Blood Adv 2019 Mar;3(6):897-907

Division of Hematology, Oncology, and Transplantation, Department of Medicine, and.

Chronic lymphocytic leukemia (CLL) is characterized by chronic clonal expansion of mature CD19-expressing B lymphocytes and global dysfunction of immune effectors, including natural killer (NK) cells. CLL remains incurable, and novel approaches to refractory CLL are needed. Our group has previously described trispecific killer engager (TriKE) molecules that redirect NK cell function against tumor cells. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018029371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436008PMC
March 2019
1 Read

T cells specific for an unconventional natural antigen fail to recognize leukemic cells.

Cancer Immunol Res 2019 Mar 19. Epub 2019 Mar 19.

Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC/UvA

MHC bound peptides from aberrant proteins may be a specific immunotherapeutic target on cancer cells. Due to difficulties in identifying such antigens, viral or model antigens have so far been used to study their biological relevance. We here identify a naturally existing human T-cell epitope derived from a truncated protein. Read More

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http://dx.doi.org/10.1158/2326-6066.CIR-18-0137DOI Listing
March 2019
4 Reads

Anti-Tumor Activity of Mannose-CpG-Oligodeoxynucleotides-Conjugated and Hepatoma Lysate-Loaded Nanoliposomes for Targeting Dendritic Cells .

J Biomed Nanotechnol 2019 May;15(5):1018-1032

Dendritic cell (DC)-based tumor vaccines are a promising immunotherapeutic method of cancer treatment. However, their therapeutic applications are significantly limited by their weak immunogenicity, costly culturing steps, and easily degradable properties. Thus, the anti-tumor activity for the vaccines should be improved. Read More

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http://dx.doi.org/10.1166/jbn.2019.2755DOI Listing

Targeting the tumor microenvironment to overcome immune checkpoint blockade therapy resistance.

Immunol Lett 2019 Mar 15. Epub 2019 Mar 15.

Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China. Electronic address:

The ability of immune checkpoint inhibitors (ICIs) to reactivate the killing function of the immune system to tumor cells has led to long lasting immune response presenting highly promising clinical advances. Recently, immune checkpoint inhibitors related resistance due to the specialized tumor microenvironment has also drawn a widely attention. To overcome resistance to immune checkpoint blockade therapy, understanding the relationship of this type of therapy and tumor microenvironment is necessary and critical. Read More

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http://dx.doi.org/10.1016/j.imlet.2019.03.006DOI Listing
March 2019
1 Read

HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1.

J Immunother Cancer 2019 Mar 18;7(1):77. Epub 2019 Mar 18.

The Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. Read More

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http://dx.doi.org/10.1186/s40425-019-0554-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421676PMC
March 2019
1 Read

Novel agents may positively impact chemotherapy and transplantation in subsets of Diffuse Large B-cell Lymphoma.

Expert Rev Hematol 2019 Mar 18. Epub 2019 Mar 18.

d Case Western Reserve University , Case Comprehensive Cancer Center , Cleveland , OH , USA .

Introduction: Molecular and biologic heterogeneity in diffuse large B-cell lymphoma (DLBCL) has resulted in a broad range of clinical outcomes. While standard frontline chemoimmunotherapy cures majority of patients with DLBCL, treatment failure in certain DLBCL subsets remains high. Prognosis in these patients is dismal. Read More

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http://dx.doi.org/10.1080/17474086.2019.1596793DOI Listing
March 2019
1 Read

Relapsed T Cell ALL: Current Approaches and New Directions.

Curr Hematol Malig Rep 2019 Mar 18. Epub 2019 Mar 18.

Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Purpose Of Review: Patients with relapsed T cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and a poor prognosis. Although a variety of salvage chemotherapy regimens may be used, response rates are unsatisfactory. This article summarizes current approaches and promising emerging strategies for the treatment of relapsed T-ALL. Read More

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http://dx.doi.org/10.1007/s11899-019-00501-3DOI Listing
March 2019
1 Read

Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors.

Front Oncol 2019 26;9:108. Epub 2019 Feb 26.

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Glypican 3 (GPC3) is a heparan sulfate proteoglycan and cell surface oncofetal protein which is highly expressed on a variety of pediatric solid embryonal tumors including the majority of hepatoblastomas, Wilms tumors, rhabdoid tumors, certain germ cell tumor subtypes, and a minority of rhabdomyosarcomas. Via both its core protein and heparan sulfate side chains, GPC3 activates the canonical Wnt/β-catenin pathway, which is frequently overexpressed in these malignancies. Loss of function mutations in lead to Simpson-Golabi-Behmel Syndrome, an X-linked overgrowth condition with a predisposition to GPC3-expressing cancers including hepatoblastoma and Wilms tumor. Read More

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http://dx.doi.org/10.3389/fonc.2019.00108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401603PMC
February 2019
4 Reads

Selective targeting of multiple myeloma by B cell maturation antigen (BCMA)-specific central memory CD8 cytotoxic T lymphocytes: immunotherapeutic application in vaccination and adoptive immunotherapy.

Leukemia 2019 Mar 12. Epub 2019 Mar 12.

Dana-Farber Cancer Institute, Boston, MA, USA.

To expand the breadth and extent of current multiple myeloma (MM)-specific immunotherapy, we have identified various antigens on CD138 tumor cells from newly diagnosed MM patients (n = 616) and confirmed B-cell maturation antigen (BCMA) as a key myeloma-associated antigen. The aim of this study is to target the BCMA, which promotes MM cell growth and survival, by generating BCMA-specific memory CD8 CTL that mediate effective and long-lasting immunity against MM. Here we report the identification of novel engineered peptides specific to BCMA, BCMA (YLMFLLRKI), and BCMA (YILWTCLGL), which display improved affinity/stability to HLA-A2 compared to their native peptides and induce highly functional BCMA-specific CTL with increased activation (CD38, CD69) and co-stimulatory (CD40L, OX40, GITR) molecule expression. Read More

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http://dx.doi.org/10.1038/s41375-019-0414-zDOI Listing
March 2019
4 Reads

An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma.

Sci Transl Med 2019 Mar;11(483)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Enthusiasm for the use of antibody-drug conjugates (ADCs) in cancer therapy has risen over the past few years. The success of this therapeutic approach relies on the identification of cell surface antigens that are widely and selectively expressed on tumor cells. Studies have shown that native ALK protein is expressed on the surface of most neuroblastoma cells, providing an opportunity for development of immune-targeting strategies. Read More

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http://dx.doi.org/10.1126/scitranslmed.aau9732DOI Listing
March 2019
1 Read

Small-Molecule Immuno-Oncology Therapy: Advances, Challenges and New Directions.

Curr Top Med Chem 2019 ;19(3):180-185

CAS Key Laboratory of Receptor Research and the State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

Oncology immunotherapy has gained significant advances in recent years and benefits cancer patients with superior efficacy and superior clinical responses. Currently over ten immune checkpoint antibodies targeting CTLA-4 and PD-1/PD-L1 have received regulatory approval worldwide and over thousands are under active clinical trials. However, compared to the rapid advance of Monoclonal Antibody (mAb), studies on immunotherapeutic small molecules have far lagged behind. Read More

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http://dx.doi.org/10.2174/1568026619666190308131805DOI Listing
April 2019
2 Reads

Ex Vivo Expanded Human Vγ9Vδ2 T-Cells Can Suppress Epithelial Ovarian Cancer Cell Growth.

Int J Mol Sci 2019 Mar 6;20(5). Epub 2019 Mar 6.

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

γδ-T-cells have attracted attention because of their potent cytotoxicity towards tumors. Most γδ-T-cells become activated via a major histocompatibility complex (MHC)-independent pathway by the interaction of their receptor, Natural Killer Group 2 Member D (NKG2D) with the tumor-specific NKG2D ligands, including MHC class I-related chain A/B (MICA/B) and UL16-binding proteins (ULBPs), to kill tumor cells. However, despite their potent antitumor effects, the treatment protocols specifically targeting ovarian tumors require further improvements. Read More

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http://dx.doi.org/10.3390/ijms20051139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429417PMC
March 2019
5 Reads

Tumor-Specific Delivery of Immune Checkpoint Inhibitors by Engineered AAV Vectors.

Front Oncol 2019 14;9:52. Epub 2019 Feb 14.

Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Langen, Germany.

Immune checkpoint inhibitors (ICIs) can block distinct receptors on T cells or tumor cells thus preventing T cell inactivation and tumor immune escape. While the clinical response to treatment with ICIs in cancer patients is impressive, this therapy is often associated with a number of immune-related adverse events. There is therefore a need to explore innovative strategies of tumor-specific delivery of ICIs. Read More

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https://www.frontiersin.org/article/10.3389/fonc.2019.00052/
Publisher Site
http://dx.doi.org/10.3389/fonc.2019.00052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382738PMC
February 2019
10 Reads

OX40 stimulation and PD-L1 blockade synergistically augment HBV-specific CD4 T cells in patients with HBeAg-negative infection.

J Hepatol 2019 Feb 28. Epub 2019 Feb 28.

Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany. Electronic address:

Background & Aims: Current antiviral therapies lack the potential to eliminate persistent hepatitis B virus (HBV) infection. HBV-specific T cells are crucial for HBV control and have recently been shown to be protective in patients following discontinuation of antiviral therapy. Thus, T cell-based approaches may greatly improve the therapeutic landscape of HBV infection. Read More

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http://dx.doi.org/10.1016/j.jhep.2019.02.016DOI Listing
February 2019
4 Reads

Salmonella-mediated therapy targeting indoleamine 2, 3-dioxygenase 1 (IDO) activates innate immunity and mitigates colorectal cancer growth.

Cancer Gene Ther 2019 Mar 1. Epub 2019 Mar 1.

Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.

Patients with colon cancer remain largely refractory to current immunotherapeutic strategies. This is, in part, due to the overexpression of the immune checkpoint protein indoleamine 2,3-dioxygenase 1 (IDO). IDO is an important enzyme contributing to tumor-mediated immunosuppression and also correlates with poor prognosis in colon cancer patients. Read More

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http://dx.doi.org/10.1038/s41417-019-0089-7DOI Listing
March 2019
3 Reads

Targeting the CINful genome: Strategies to overcome tumor heterogeneity.

Prog Biophys Mol Biol 2019 Feb 25. Epub 2019 Feb 25.

Department of Pathology, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, S7N 5E5 Canada; Cancer Research, Saskatchewan Cancer Agency, 107 Wiggins Road, Saskatoon, S7N 5E5, Canada. Electronic address:

Genomic instability, and more specifically chromosomal instability (CIN), arises from a number of processes that are defective in cancer, such as aberrant mitotic cell division, replication stress, defective DNA damage repair, and ineffective telomere maintenance. CIN is an emerging hallmark of cancer that contributes to tumor heterogeneity through increased rates of genetic alterations. As genetic heterogeneity within a single tumor and between tumors is a key challenge leading to treatment failures, this brings to question, whether therapeutic approaches should aim at the genetic diversity or a specific mutation present within these tumors. Read More

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http://dx.doi.org/10.1016/j.pbiomolbio.2019.02.006DOI Listing
February 2019

Applications of SNAP-tag technology in skin cancer therapy.

Health Sci Rep 2019 Feb 8;2(2):e103. Epub 2019 Jan 8.

Department of Integrative Biomedical Sciences, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences University of Cape Town Cape Town South Africa.

Background: Cancer treatment in the 21st century has seen immense advances in optical imaging and immunotherapy. Significant progress has been made in the bioengineering and production of immunoconjugates to achieve the goal of specifically targeting tumors.

Discussion: In the 21st century, antibody drug conjugates (ADCs) have been the focus of immunotherapeutic strategies in cancer. Read More

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http://dx.doi.org/10.1002/hsr2.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375544PMC
February 2019
4 Reads

Surface-Layer Protein-Enhanced Immunotherapy Based on Cell Membrane-Coated Nanoparticles for the Effective Inhibition of Tumor Growth and Metastasis.

ACS Appl Mater Interfaces 2019 Mar 4;11(10):9850-9859. Epub 2019 Mar 4.

Department of Chemistry , Zhejiang University , Hangzhou 310028 , China.

Chemo-immunotherapy is an important tool to overcome tumor immune suppression in cancer immunotherapy. Herein, we report a surface-layer (S-layer) protein-enhanced immunotherapy strategy based on cell membrane-coated S-CM-HPAD nanoparticles for the effective malignant tumor therapy and metastasis inhibition. The S-CM-HPAD NPs could effectively deliver the tumor antigen, DOX, and immunoadjuvant to the homotypic tumor by the homotypic targeting ability of the coated cell membrane. Read More

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http://dx.doi.org/10.1021/acsami.9b00294DOI Listing
March 2019
1 Read
6.723 Impact Factor

Quantifying Antigen-Specific T Cell Responses When Using Antigen-Agnostic Immunotherapies.

Mol Ther Methods Clin Dev 2019 Jun 29;13:154-166. Epub 2019 Jan 29.

Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

Immunotherapies are at the forefront of the fight against cancers, and researchers continue to develop and test novel immunotherapeutic modalities. Ideal cancer immunotherapies induce a patient's immune system to kill their own cancer and develop long-lasting immunity. Research has demonstrated a critical requirement for CD8 and CD4 T cells in achieving durable responses. Read More

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http://dx.doi.org/10.1016/j.omtm.2019.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369252PMC

design of a triple-negative breast cancer vaccine by targeting cancer testis antigens.

Bioimpacts 2019 2;9(1):45-56. Epub 2018 Jul 2.

Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

Triple-negative breast cancer (TNBC) is an important subtype of breast cancer, which occurs in the absence of estrogen, progesterone and HER-2 receptors. According to the recent studies, TNBC may be a cancer testis antigen (CTA)-positive tumor, indicating that the CTA-based cancer vaccine can be a treatment option for the patients bearing such tumors. Of these antigens (Ags), the MAGE-A family and NY-ESO-1 as the most immunogenic CTAs are the potentially relevant targets for the development of an immunotherapeutic way of the breast cancer treatment. Read More

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http://dx.doi.org/10.15171/bi.2019.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378095PMC

The ATP-Binding Cassette Gene ABCF1 Functions as an E2 Ubiquitin-Conjugating Enzyme Controlling Macrophage Polarization to Dampen Lethal Septic Shock.

Immunity 2019 Feb 12;50(2):418-431.e6. Epub 2019 Feb 12.

Michael Smith Laboratories, University of British Columbia (UBC), 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada; The Vancouver Prostate Centre, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada; Department of Microbiology and Immunology, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Centre for Blood Research, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Department of Zoology, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Department of Medical Genetics, UBC, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada; Djavad Mowafaghian Centre for Brain Health, 2215 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. Electronic address:

Sepsis is a bi-phasic inflammatory disease that threatens approximately 30 million lives and claims over 14 million annually, yet little is known regarding the molecular switches and pathways that regulate this disease. Here, we have described ABCF1, an ATP-Binding Cassette (ABC) family member protein, which possesses an E2 ubiquitin enzyme activity, through which it controls the Lipopolysaccharide (LPS)- Toll-like Receptor-4 (TLR4) mediated gram-negative insult by targeting key proteins for K63-polyubiquitination. Ubiquitination by ABCF1 shifts the inflammatory profile from an early phase MyD88-dependent to a late phase TRIF-dependent signaling pathway, thereby regulating TLR4 endocytosis and modulating macrophage polarization from M1 to M2 phase. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.01.014DOI Listing
February 2019
3 Reads

CXCR4 and PD-1 Expression in Head and Neck Cancer with Perineural Spread.

J Neurol Surg B Skull Base 2019 Feb 14;80(1):18-22. Epub 2018 Jun 14.

School of Medicine, University of Queensland, Brisbane, Queensland, Australia.

 Perineural spread (PNS) is a marker of aggressiveness and has been shown to occur in cranial nerves due to advanced mucosal and cutaneous head and neck cancer. Receptors CXC chemokine receptor 4 (CXCR4) and programmed cell death-1 (PD-1) have been shown to be overexpressed in a variety of cancers with PNS, with the inhibition of these pathways offering a potential future treatment.  Retrospective immunohistochemical staining for the CXCR4 and PD-1 receptors was performed on 28 head and neck specimens that demonstrated PNS from January 2017 to August 2017, at Royal Brisbane and Women's Hospital, Brisbane, Australia. Read More

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http://www.thieme-connect.de/DOI/DOI?10.1055/s-0038-1660846
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http://dx.doi.org/10.1055/s-0038-1660846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365291PMC
February 2019
9 Reads

HDAC6 selective inhibition of melanoma patient T-cells augments anti-tumor characteristics.

J Immunother Cancer 2019 Feb 6;7(1):33. Epub 2019 Feb 6.

NYU Langone Health, 522 First Avenue, 1306 Smilow Research Building, New York, NY, 10016, USA.

Background: Therapies targeting anti-tumor T-cell responses have proven successful in the treatment of a variety of malignancies. However, as most patients still fail to respond, approaches to augment immunotherapeutic efficacy are needed. Here, we investigated the ability of histone deacetylase 6 (HDAC6)-selective inhibitors to decrease immunosuppression and enhance immune function of melanoma patient T-cells in ex vivo cultures. Read More

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http://dx.doi.org/10.1186/s40425-019-0517-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366050PMC
February 2019
1 Read

A strategy for generating cancer-specific monoclonal antibodies to aberrant O-glycoproteins: identification of a novel dysadherin-Tn antibody.

Glycobiology 2019 04;29(4):307-319

Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen N, Denmark.

Successful application of potent antibody-based T-cell engaging immunotherapeutic strategies is currently limited mainly to hematological cancers. One major reason is the lack of well-characterized antigens on solid tumors with sufficient cancer specific expression. Aberrantly O-glycosylated proteins contain promising cancer-specific O-glycopeptide epitopes suitable for immunotherapeutic applications, but currently only few examples of such antibody epitopes have been identified. Read More

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http://dx.doi.org/10.1093/glycob/cwz004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430981PMC
April 2019
1 Read

New approach for cancer immunotherapy based on the cancer stem cell antigens properties.

Curr Mol Med 2019 Feb 3. Epub 2019 Feb 3.

Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz. Iran.

Background: Cancer stem cells (CSCs) are a rare population of tumor cells, which play an important role in tumor initiation, progression, and maintenance. The concept that cancer cells arise from stem cells was presented about 150 years ago. Nowadays, because of the heterogeneity of tumor cells, this hypothesis has been renewed. Read More

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http://www.eurekaselect.com/169602/article
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http://dx.doi.org/10.2174/1566524019666190204114721DOI Listing
February 2019
11 Reads

Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma.

Cancers (Basel) 2019 Jan 24;11(2). Epub 2019 Jan 24.

Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.

Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. Read More

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http://www.mdpi.com/2072-6694/11/2/137
Publisher Site
http://dx.doi.org/10.3390/cancers11020137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406711PMC
January 2019
10 Reads

Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter.

Ther Adv Urol 2019 Jan-Dec;11:1756287218815372. Epub 2019 Jan 8.

Section of Pathological Anatomy, Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, Ancona, Marche, I-60126, Italy.

Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1-2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Read More

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http://dx.doi.org/10.1177/1756287218815372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329040PMC
January 2019
17 Reads

Immunotherapeutic Approaches for Multiple Myeloma: Where Are We Now?

Authors:
Myo Htut

Curr Hematol Malig Rep 2019 Feb;14(1):1-10

Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA.

Purpose Of Review: The treatment landscape for multiple myeloma has evolved rapidly with the availability of multiple new drugs; however, although patient survival has improved, the disease remains incurable. Multiple myeloma is characterized by the unregulated growth of malignant plasma cells accompanied by immune dysfunction as well as disrupted immune surveillance mechanisms. Here, we analyze clinical modalities, with a focus on monoclonal antibodies and adoptive cellular therapy that enhance patients' immune systems and overcome these defects. Read More

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http://dx.doi.org/10.1007/s11899-019-0492-zDOI Listing
February 2019
1 Read

A therapeutic vaccine targeting HPV E6/E7 with intrinsic Toll-like receptor 2 agonist activity induces antitumor immunity.

Am J Cancer Res 2018 1;8(12):2528-2537. Epub 2018 Dec 1.

Graduate Institute of Biomedical Sciences, China Medical University Taichung, Taiwan.

The E6 and E7 oncoproteins of human papillomavirus (HPV) are ideal targets for developing immunotherapeutic approaches to treat HPV-associated tumors. Our previous studies showed that a recombinant lipidated HPV16 E7 mutant (rlipo-E7m) with inactivation of the E7 oncogenic functions can activate antigen presenting cells through Toll-like receptor 2 (TLR2) and induce antitumor immunity. Given that some HPV-associated tumors overexpress E6 but not E7, it is necessary to include therapeutic agents containing HPV E6 in therapeutic vaccine development to broaden the utility of the vaccine. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325468PMC
December 2018
1 Read

Novel fusion cells derived from tumor cells expressing the heterologous α-galactose epitope and dendritic cells effectively target cancer.

Vaccine 2019 Feb 17;37(7):926-936. Epub 2019 Jan 17.

School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China; Intenational Nanobody Research Center of Guangxi, Guangxi Medical University, Nanning, Guangxi 530021, China; National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China. Electronic address:

Tumor cells/dendritic cells (DCs) fusion cells (tumor/DC) represent a promising immunotherapeutic strategy but are still under performed in clinical trials for cancer treatment. To further boost their anticancer efficacy, here we developed a novel design for fusing dendritic cells with MDA-MB-231 cells expressing the heterologous α-galactose (α-gal) epitope and assessed its anticancer activities both in vitro and in vivo. The high expression of α-gal in MDA-MB-231 (Gal)/DC correlated with enhanced DC activation. Read More

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http://dx.doi.org/10.1016/j.vaccine.2019.01.004DOI Listing
February 2019
3 Reads

Vascular Targeting to Increase the Efficiency of Immune Checkpoint Blockade in Cancer.

Front Immunol 2018 21;9:3081. Epub 2018 Dec 21.

Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, The Rudbeck Laboratory, Uppsala, Sweden.

Boosting natural immunity against malignant cells has had a major breakthrough in clinical cancer therapy. This is mainly due to the successful development of immune checkpoint blocking antibodies, which release a break on cytolytic anti-tumor-directed T-lymphocytes. However, immune checkpoint blockade is only effective for a proportion of cancer patients, and a major challenge in the field is to understand and overcome treatment resistance. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2018.03081
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http://dx.doi.org/10.3389/fimmu.2018.03081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309238PMC
December 2018
11 Reads

Novel Vaccine Targeting Colonic Adenoma: a Pre-clinical Model.

J Gastrointest Surg 2019 Mar 8;23(3):626-633. Epub 2019 Jan 8.

Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the USA. Over 80% of CRC develop from adenomatous polyps. Hence, early treatment and prevention of adenomas would lead to a significant decrease of disease burden for CRC. Read More

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http://link.springer.com/10.1007/s11605-018-4060-y
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http://dx.doi.org/10.1007/s11605-018-4060-yDOI Listing
March 2019
22 Reads

Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load.

Gut 2019 05 8;68(5):905-915. Epub 2019 Jan 8.

Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.

Objective: A hallmark of chronic HBV (cHBV) infection is the presence of impaired HBV-specific CD8+ T cell responses. Functional T cell exhaustion induced by persistent antigen stimulation is considered a major mechanism underlying this impairment. However, due to their low frequencies in chronic infection, it is currently unknown whether HBV-specific CD8+ T cells targeting different epitopes are similarly impaired and share molecular profiles indicative of T cell exhaustion. Read More

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http://dx.doi.org/10.1136/gutjnl-2018-316641DOI Listing
May 2019
13 Reads

Breech at the Border: An Atypical Case of Invasive in a Patient on a Novel Immunotherapeutic.

Open Forum Infect Dis 2018 Jul 26;5(7):ofy146. Epub 2018 Jun 26.

Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

e rarely causes pyogenic infections in the female genital tract, and even less commonly does this lead to systemic infections. Novel monoclonal antibody therapies targeting interleukin-17 may impair mucosal immunity, but increased risk for e infections has not been documented. Here, we describe a case of e bacteremia associated with pyosalpinx and hypothesize that immunomodulatory treatment for psoriasis predisposed our patient to this infection. Read More

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http://dx.doi.org/10.1093/ofid/ofy146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299461PMC
July 2018
7 Reads

Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection.

Gut 2019 05 22;68(5):893-904. Epub 2018 Dec 22.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Objective: Chronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Read More

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http://dx.doi.org/10.1136/gutjnl-2018-316644DOI Listing
May 2019
4 Reads