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https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#1
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#2
REVIEW
Jacek Mackiewicz, Andrzej Mackiewicz
The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28434400/role-of-modern-immunotherapy-in-gastrointestinal-malignancies-a-review-of-current-clinical-progress
#3
REVIEW
Zin W Myint, Gaurav Goel
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434399/the-next-generation-of-immunotherapy-keeping-lung-cancer-in-check
#4
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28428880/long-term-complete-remission-with-ipilimumab-in-metastatic-castrate-resistant-prostate-cancer-case-report-of-two-patients
#5
Luc Cabel, Elika Loir, Gwenaelle Gravis, Pernelle Lavaud, Christophe Massard, Laurence Albiges, Giulia Baciarello, Yohann Loriot, Karim Fizazi
BACKGROUND: Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28426103/neurotoxicity-from-immune-checkpoint-inhibition-in-the-treatment-of-melanoma-a-single-centre-experience-and-review-of-the-literature
#6
L Spain, G Walls, M Julve, K O'Meara, T Schmid, E Kalaitzaki, S Turajlic, M Gore, J Rees, J Larkin
Background: Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase III trials. Immune-related neurological toxicity of varying severity has been reported in the literature. The cumulative incidence of neurotoxicity among ipilimumab, nivolumab and pembrolizumab is reported as <1% in published clinical trials. We aimed to identify the incidence of neurotoxicity in our institution across anti-CTLA4 and anti-PD-1 antibodies, including the combination of ipilimumab with nivolumab...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlates-with-response-in-head-and-neck-cancer-patients
#7
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8+ tumorinfiltrating lymphocytes (TILs) and compared them to those of peripheral blood T lymphocytes (PBLs) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
April 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28403786/immune-checkpoint-inhibitors-and-cardiac-toxicity-an-emerging-issue
#8
Gilda Varricchi, Giancarlo Marone, Valentina Mercurio, Maria Rosaria Galdiero, Domenico Bonaduce, Carlo G Tocchetti
Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Cancer immunotherapies over the last years have revolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis...
April 7, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28401596/successful-retreatment-with-combined-braf-mek-inhibition-in-metastatic-brafv600-mutated-melanoma
#9
Valerie C Amann, Dorothée Hoffmann, Joanna Mangana, Reinhard Dummer, Simone M Goldinger
BACKGROUND: The combination treatment with BRAF- and MEK-inhibitors is amongst the current standard of care for stage IIIC/IV BRAF-mutated melanoma. However, therapeutic options are limited once patients have progressed upon both targeted and immunotherapy. OBJECTIVE: To investigate whether retreatment with BRAF- and MEK-inhibitor combination is an option for patients with metastatic BRAF-mutated melanoma upon previous progression on kinase inhibitors. METHODS: Two patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF- and MEK-inhibitor combination after progression on targeted therapy and subsequent immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies...
April 12, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28401456/cardiovascular-complications-associated-with-novel-cancer-immunotherapies
#10
REVIEW
Varun Jain, Jaspreet Bahia, Mahsa Mohebtash, Ana Barac
Immune therapies represent a quantum leap in the fight against cancer. Recently approved immune checkpoint inhibitors that target receptors involved in immune escape of cancer cells (including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death protein ligand-1 (PD-L1) are increasingly being used for therapeutic benefit in a number of cancers. The robust anti-cancer activity of these agents has been accompanied by the recognition of new adverse effects, often due to the over activation of immune system, that may limit their therapeutic benefit and adversely impact outcomes...
May 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28397508/an-autoimmune-haemolytic-anaemia-secondary-to-ipilimumab-treatment
#11
B Ramos, G Gastal, R K Rovere
BACKGROUND: Melanoma is one of the fastest growing neoplasms worldwide. Treatment of metastatic disease has swiftly shifted in the last decade from generally ineffective chemotherapy regimens to highly effective targeted treatments or immunotherapy, with a range of side effects that differ completely from those of previous treatments for this disease. CASE: We present a case of a 71-year-old man with diagnosis metastatic melanoma. This patient was treated with anti-CTLA-4 antibody ipilimumab...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28383639/immune-checkpoint-inhibitors-in-advanced-renal-cell-carcinoma-experience-to-date-and-future-directions
#12
M B Atkins, J I Clark, D I Quinn
In recent years, there has been dramatic expansion of the treatment armamentarium for patients with advanced renal cell carcinoma (aRCC), including drugs targeting vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. Despite these advances, patient outcomes remain suboptimal, underscoring the need for therapeutic interventions with novel mechanisms of action. The advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment landscape for several solid malignancies...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28374786/targeted-agents-and-immunotherapies-optimizing-outcomes-in-melanoma
#13
REVIEW
Jason J Luke, Keith T Flaherty, Antoni Ribas, Georgina V Long
Treatment options for patients with metastatic melanoma, and especially BRAF-mutant melanoma, have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents. During this period, the treatment paradigm for BRAF-mutant disease has evolved rapidly: the standard-of-care BRAF-targeted approach has shifted from single-agent BRAF inhibition to combination therapy with a BRAF and a MEK inhibitor. Concurrently, immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and, now, the programmed cell-death protein 1 (PD-1) immune checkpoints...
April 4, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28369782/immune-checkpoint-proteins-exploring-their-therapeutic-potential-to-regulate-atherosclerosis
#14
REVIEW
A C Foks, J Kuiper
The immune system provides a large diversity of immune checkpoint proteins, which involve both costimulatory and inhibitory proteins. Costimulatory proteins can promote cell survival, cell cycle progression and differentiation to effector and memory cells, whereas inhibitory proteins terminate these processes to halt ongoing inflammation. Immune checkpoint proteins play a pivotal role in atherosclerosis by regulating the activation and proliferation of various immune and non-immune cells, such as T cells, macrophages and platelets...
March 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28363614/acute-symptomatic-hypocalcemia-from-immune-checkpoint-therapy-induced-hypoparathyroidism
#15
Myint Aung Win, Kyaw Zin Thein, Aiham Qdaisat, Sai-Ching Jim Yeung
BACKGROUND: Ipilimumab (a monoclonal antibody against CTLA-4) and nivolumab (a humanized antibody against PD-1) target these immune checkpoint pathways and are used for treatment of melanoma and an increasing number of other cancers. However, they may cause immune-related adverse effects (IRAEs). Although many endocrinopathies are known to be IRAEs, primary hypoparathyroidism with severe hypocalcemia has never been reported. This is the first case of hypoparathyroidism as an IRAE presenting to an Emergency Department with acute hypocalcemia...
February 27, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28362496/near-infrared-triggered-photodynamic-therapy-with-multi-tasking-upconversion-nanoparticles-in-combination-with-checkpoint-blockade-for-immunotherapy-of-colorectal-cancer
#16
Jun Xu, Ligeng Xu, Chenya Wang, Rong Yang, Qi Zhuang, Xiao Han, Ziliang Dong, Wenwen Zhu, Rui Peng, Zhuang Liu
While immunotherapy has become a highly promising paradigm for cancer treatment in recent years, it has long been recognized that photodynamic therapy (PDT) has the ability to trigger antitumor immune responses. However, conventional PDT triggered by visible light has limited penetration depth, and its generated immune responses may not be robust enough to eliminate tumors. Herein, upconversion nanoparticles (UCNPs) are simultaneously loaded with chlorin e6 (Ce6), a photosensitizer, and imiquimod (R837), a Toll-like-receptor-7 agonist...
March 31, 2017: ACS Nano
https://www.readbyqxmd.com/read/28359471/targeting-immune-checkpoints-in-esophageal-cancer-a-high-mutational-load%C3%A2-tumor
#17
REVIEW
Rajeev Dhupar, Lauren Van Der Kraak, Arjun Pennathur, Matthew J Schuchert, Katie S Nason, James D Luketich, Michael T Lotze
Checkpoint inhibitors (eg, programmed cell death protein 1 [PD-1], programmed cell death ligand 1 [PD-L1], cytotoxic T-lymphocyte associated protein 4 [CTLA-4] antibodies) are changing how we understand cancer and provide a means to develop modern immunotherapies. An emergent notion relates success with checkpoint inhibitors with high mutational load tumors. There are few studies that examine checkpoint protein expression and relate these to clinical outcomes after the conventional treatment of patients with esophageal cancer, which has a high mutational load...
April 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28357489/molecular-genetic-and-immunotherapeutic-targets-in-metastatic-melanoma
#18
REVIEW
C Melis, A Rogiers, O Bechter, Joost J van den Oord
In recent years, melanoma treatment has radically changed with the emergence of targeted therapies and immunotherapies. Both have led to improved survival for patients with advanced or unresectable melanoma. Targeted therapies with BRAF inhibitors in the lead use the presence of activating driver mutations to inhibit tumour growth. Forty to 60% of melanomas harbour BRAF mutations, which makes them susceptible to treatment with BRAF and/or MEK inhibitors. In parallel, the development of immunotherapeutic agents has also expanded...
March 29, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28356263/profiling-response-resistance-to-immunotherapy
#19
(no author information available yet)
In a longitudinal analysis of patients with metastatic melanoma who received sequential therapies targeting CTLA-4, then PD-1 upon disease progression, researchers have discovered that high copy-number loss in recurrent regions of the tumor genome is associated with resistance to immune checkpoint blockade.
March 29, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28351930/hyper-progressors-after-immunotherapy-analysis-of-genomic-alterations-associated-with-accelerated-growth-rate
#20
Shumei Kato, Aaron Michael Goodman, Vighnesh Walavalkar, Donald A Barkauskas, Andrew Sharabi, Razelle Kurzrock
PURPOSE: Checkpoint inhibitors demonstrate salutary anti-cancer effects including long-term remissions. PD-L1 expression/amplification, high mutational burden and mismatch repair-deficiency correlate with response. We have, however, observed a subset of patients who appear to be "hyper-progressors," with a greatly accelerated rate of tumor growth and clinical deterioration compared to pre-therapy, which was also recently reported by Institut Gustave Roussy. The current study investigated potential genomic markers associated with "hyper-progression" after immunotherapy...
March 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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