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immune-checkpoint blockade

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https://www.readbyqxmd.com/read/27910704/the-safety-of-nivolumab-for-the-treatment-of-advanced-non-small-cell-lung-cancer
#1
Giulio Metro, Biagio Ricciuti, Marta Brambilla, Sara Baglivo, Irene Soli, Elisa Minenza, Giulia Costanza Leonardi, Alessandro D'Arpino, Daniela Colabrese, Marco Tazza, Daniela Zicari, Vincenzo Minotti, Rita Chiari
Immune checkpoint blockaders (ICBs) act by unbalancing the immune system, thus favoring the development of an immune-mediated antitumor effect. ICBs targeting the programmed cell death receptor-1 (PD-1) have recently been investigated in a number of advanced tumors, including non-small cell lung cancer (NSCLC). Nivolumab, a fully human IgG4 kappa directed against PD-1, has been the first ICB to be approved for second-line treatment of advanced NSCLC. Areas covered: In this review we focus on the clinical development of nivolumab for the treatment of advanced NSCLC, with an emphasis on its safety profile...
December 2, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27905822/uterine-cancer-mutational-phenotype-and-the-era-of-immune-checkpoint-blockade
#2
Dana M Roque, Alessandro D Santin
No abstract text is available yet for this article.
December 1, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#3
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904752/the-role-of-immune-checkpoint-inhibition-in-the-treatment-of-ovarian-cancer
#4
REVIEW
Stéphanie L Gaillard, Angeles A Secord, Bradley Monk
The introduction of immune checkpoint inhibitors has revolutionized treatment of multiple cancers and has bolstered interest in this treatment approach. So far, emerging clinical data show limited clinical efficacy of these agents in ovarian cancer with objective response rates of 10-15% with some durable responses. In this review, we present emerging clinical data of completed trials of immune checkpoint inhibitors and review ongoing studies. In addition we examine the current knowledge of the tumor microenvironment of ovarian cancers with a focus on the significance of PD-L1 expression and tumor-infiltrating lymphocytes on predicting response to immune checkpoint blockade...
2016: Gynecologic Oncology Research and Practice
https://www.readbyqxmd.com/read/27899772/-lung-cancer
#5
Kazushi Yoshida, Takashi Kono
Personalized lung cancer therapy has progressed by targeting several oncogenic aberrations that drive lung carcinogenesis. Recent advances in gene analysis technologies, including next-generation sequencing that yields large amounts of genomic data, have greatly contributed to this progress. In addition, immune checkpoint blockade therapy has become available in Japan, and extensive searches for biomarkers predictive of therapeutic response have been carried out. "Clinical sequencing" which analyzes aberrations in a set of therapy-related genes in patient cancer specimens, has been actively conducted in Japan and other countries...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27895917/validation-of-biomarkers-to-predict-response-to-immunotherapy-in-cancer-volume-i-pre-analytical-and-analytical-validation
#6
REVIEW
Giuseppe V Masucci, Alessandra Cesano, Rachael Hawtin, Sylvia Janetzki, Jenny Zhang, Ilan Kirsch, Kevin K Dobbin, John Alvarez, Paul B Robbins, Senthamil R Selvan, Howard Z Streicher, Lisa H Butterfield, Magdalena Thurin
Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successes in a variety of malignancies, responses only typically occur in a minority of patients in any given histology. Additionally, treatment is associated with inflammatory toxicity and high cost...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27892653/low-baseline-levels-of-nk-cells-may-predict-a-positive-response-to-ipilimumab-in-melanoma-therapy
#7
Julia K Tietze, Daniela Angelova, Markus V Heppt, Thomas Ruzicka, Carola Berking
The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T cell populations has been studied extensively but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56(dim) and CD56(bright) NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27889032/metastatic-anal-cancer-and-novel-agents
#8
REVIEW
Van Morris, Cathy Eng
Squamous cell carcinoma of the anal canal (SCCA) represents an orphan disease. Although prior infection with human papilloma virus is associated with the development of SCCA, knowledge of this relationship has proven ineffective in identifying therapeutic agents that have activity in the management of metastatic SCCA. Combination chemotherapy with traditional cytotoxic agents has demonstrated efficacy in multiple small series. However, immune checkpoint blockade agents have demonstrated efficacy for patients with refractory metastatic SCCA; these agents hold promise in the horizon for patients with metastatic SCCA...
January 2017: Surgical Oncology Clinics of North America
https://www.readbyqxmd.com/read/27888981/emerging-role-of-immunotherapy-in-urothelial-carcinoma-advanced-disease
#9
REVIEW
Matthew Zibelman, Chethan Ramamurthy, Elizabeth R Plimack
Systemic therapy for metastatic urothelial carcinoma has seen minimal progress and no new approved therapies in the past 20 years. However, with the approval of the checkpoint inhibitor atezolizumab in May 2016, immunotherapy inserted itself into the standard clinical dogma. The emergence of systemic immunotherapies, heralded by drugs targeting immune checkpoint blockade, can provide durable remissions in a subset of patients with a favorable toxicity profile. With other similar agents showing promise in early-phase trials, more options may be on the way...
December 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27882779/ipilimumab-from-preclinical-development-to-future-clinical-perspectives-in-melanoma
#10
Paul Letendre, Varun Monga, Mohammed Milhem, Yousef Zakharia
The arsenal for the treatment of metastatic melanoma is limited. A new approach to therapy using checkpoint blockade has improved overall survival in this patient population. Ipilimumab a CTLA-4 monoclonal antibody is a first in class drug that has pioneered this revolution. In this review, the authors provide an account of the different stages that led to the development of ipilimumab, its approval in the clinical setting for the treatment of advanced melanoma and ongoing investigations of combinatorial immune therapy...
November 24, 2016: Future Oncology
https://www.readbyqxmd.com/read/27879972/responses-of-metastatic-basal-cell-and-cutaneous-squamous-cell-carcinomas-to-anti-pd1-monoclonal-antibody-regn2810
#11
Gerald S Falchook, Rom Leidner, Elizabeth Stankevich, Brian Piening, Carlo Bifulco, Israel Lowy, Matthew G Fury
BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) share exposure to UV light as the dominant risk factor, and these tumors therefore harbor high mutation burdens. In other malignancies, high mutation burden has been associated with clinical benefit from therapy with antibodies directed against the Programmed Death 1 (PD-1) immune checkpoint receptor. Highly mutated tumors are more likely to express immunogenic tumor neoantigens that attract effector T cells, which can be unleashed by blockade of the PD-1 immune checkpoint...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27874062/systemic-perioperative-management-of-muscle-invasive-bladder-cancer-and-future-horizons
#12
REVIEW
Samuel A Funt, Jonathan E Rosenberg
Many patients diagnosed with muscle-invasive bladder cancer (MIBC) will develop distant metastatic disease. Over the past three decades, perioperative cisplatin-based chemotherapy has been investigated for its ability to reduce the number of deaths from bladder cancer. Insufficient evidence is available to fully support the use of such chemotherapy in the adjuvant setting; however, neoadjuvant cisplatin-based combination chemotherapy has become a standard of care for eligible patients based on the improved disease-specific and overall survival demonstrated in two randomized phase III trials, compared with surgery alone...
November 22, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27873300/local-checkpoint-inhibition-of-ctla-4-as-a-monotherapy-or-in-combination-with-anti-pd1-prevents-the-growth-of-murine-bladder-cancer
#13
Luuk van Hooren, Linda C Sandin, Igor Moskalev, Peter Ellmark, Anna Dimberg, Peter Black, Thomas H Tötterman, Sara M Mangsbo
Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in metastatic cancer patients. However, patients treated with CTLA-4 blockade have suffered from immune related adverse events, most likely due to the breadth of the induced T-cell activation. Here, we investigated the efficacy of a local low-dose anti-CTLA-4 administration for treatment of subcutaneous or orthotopic MB49 bladder carcinoma in C57BL/6 mice. When MB49 tumors were grown subcutaneously, peritumoral injection of anti-CTLA-4 treatment was equally effective as intravenous or subcutaneous (non-tumor bearing flank) administration...
November 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27873079/next-generation-predictive-biomarkers-for-immune-checkpoint-inhibition
#14
Yulian Khagi, Razelle Kurzrock, Sandip Pravin Patel
With the advent of targeted therapies, there has been a revolution in the treatment of cancer across multiple histologies. Immune checkpoint blockade has made it possible to take advantage of receptor-ligand interactions between immune and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue, however, can limit our use of these agents. Immune checkpoint blockade has been approved in advanced melanoma, renal cell cancer, non-small cell lung cancer, relapsed refractory Hodgkin's lymphoma, and urothelial cancer...
November 21, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27872096/polyi-c-and-cpg-synergize-with-anti-erbb2-mab-for-treatment-of-breast-tumors-resistant-to-immune-checkpoint-inhibitors
#15
Roxanne Charlebois, Bertrand Allard, David Allard, Laurence Buisseret, Martin Turcotte, Sandra Pommey, Pavel Chrobak, John Stagg
Innate and adaptive immune cells play an important role in the therapeutic activity of anti-ErbB2 mAbs such as trastuzumab. In the clinic, breast tumors poorly infiltrated with immune cells are more resistant to trastuzumab and patients have a worse prognosis. Because type I and II interferons (IFNs) are critical to the immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory response in breast tumors able to induce long lasting CD8+ T cell-dependent anti-tumor immunity...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27864231/pi3k%C3%AE-inhibition-potentiates-immune-checkpoint-blockade
#16
(no author information available yet)
Targeting PI3Kγ overcomes myeloid cell-mediated resistance to immune checkpoint blockade.
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27861370/preferences-of-german-melanoma-patients-for-interferon-ifn-%C3%AE-2b-toxicities-the-decog-germelatox-survey-versus-melanoma-recurrence-to-quantify-patients-relative-values-for-adjuvant-therapy
#17
Katharina C Kaehler, Christine Blome, Andrea Forschner, Ralf Gutzmer, Thomas Haalck, Lucie Heinzerling, Thomas Kornek, Elisabeth Livingstone, Carmen Loquai, Lara Valeska Maul, Berenice M Lang, Dirk Schadendorf, Barbara Stade, Patrick Terheyden, Jochen Utikal, Tobias Wagner, Axel Hauschild, Claus Garbe, Matthias Augustin
Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNα has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27859479/diverse-types-of-dermatologic-toxicities-from-immune-checkpoint-blockade-therapy
#18
REVIEW
Jonathan L Curry, Michael T Tetzlaff, Priyadharsini Nagarajan, Carol Drucker, Adi Diab, Sharon R Hymes, Madeleine Duvic, Wen-Jen Hwu, Jennifer A Wargo, Carlos A Torres-Cabala, Ronald P Rapini, Victor G Prieto
Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells has been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade...
November 10, 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27856600/tti-621-sirp%C3%AE-fc-a-cd47-blocking-innate-immune-checkpoint-inhibitor-with-broad-anti-tumor-activity-and-minimal-erythrocyte-binding
#19
Penka S Petrova, Natasja N Viller, Mark Wong, Xinli Pang, Gloria H Y Lin, Karen Dodge, Vien Chai, Hui Chen, Vivian Lee, Violetta House, Noel T Vigo, Debbie Jin, Tapfuma Mutukura, Marilyse Charbonneau, Tran Truong, Stéphane Viau, Lisa D Johnson, Emma Linderoth, Eric L Sievers, Saman Maleki Vareki, Rene Figueredo, Macarena Pampillo, James Koropatnick, Suzanne Trudel, Nathan Mbong, Liqing Jin, Jean C Y Wang, Robert A Uger
PURPOSE: The ubiquitously expressed transmembrane glycoprotein CD47 delivers an anti-phagocytic (do-not-eat) signal by binding signal-regulatory protein α (SIRPα) on macrophages. CD47 is over-expressed in cancer cells and its expression is associated with poor clinical outcomes. TTI 621 (SIRPαFc) is a fully human recombinant fusion protein that blocks the CD47:SIRPα-axis by binding to human CD47 and enhancing phagocytosis of malignant cells. Blockade of this inhibitory axis using TTI-621 has emerged as a promising therapeutic strategy to promote tumor cell eradication...
November 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27856426/cytotoxic-t-cells-in-pd-l1-positive-malignant-pleural-mesotheliomas-are-counterbalanced-by-distinct-immunosuppressive-factors
#20
Mark M Awad, Robert E Jones, Hongye Liu, Patrick H Lizotte, Elena V Ivanova, Meghana Kulkarni, Grit S Herter-Sprie, Xiaoyun Liao, Abigail A Santos, Mark A Bittinger, Lauren Keogh, Shohei Koyama, Christina Almonte, Jessie M English, Julianne Barlow, William G Richards, David A Barbie, Adam J Bass, Scott J Rodig, F Stephen Hodi, Kai W Wucherpfennig, Pasi A Jänne, Lynette M Sholl, Peter S Hammerman, Kwok-Kin Wong, Raphael Bueno
PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens...
December 2016: Cancer Immunology Research
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