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Melanoma pd-1

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https://www.readbyqxmd.com/read/29666298/delayed-autoimmune-toxicity-occurring-several-months-after-cessation-of-anti-pd-1-therapy
#1
Sagun Parakh, Jonathan Cebon, Oliver Klein
Treatment with anti-programmed cell death protein 1 (PD-1) antibodies has demonstrated clinical efficacy in a whole range of malignancies including advanced melanoma, renal cell cancer, bladder cancer, and non-small cell lung cancer. Immune-related adverse events are a unique side effect of checkpoint regulator therapy including anti-PD-1 antibodies. Treatment-related autoimmunity can occur in any organ system, with the median onset usually within 5-15 weeks from the commencement of therapy, depending on the organ system involved...
April 17, 2018: Oncologist
https://www.readbyqxmd.com/read/29665734/in-vivo-antitumor-effects-of-mk615-led-by-pd-l1-downregulation
#2
Masashi Yanaki, Masayuki Kobayashi, Atsushi Aruga, Minoru Nomura, Makoto Ozaki
BACKGROUND/AIM: MK615 extracted from Prunus mume was reported to have anti-inflammatory effects. In this article, we examined the in vivo antitumor effect of MK615 (an extract from Japanese apricot) using mouse tumor xenografts and focusing on the downregulation of PD-L1 (programmed death-ligand 1), a ligand of programmed cell death-1, a surface protein of activated T cells. MATERIALS AND METHODS: B16/BL6 melanoma cells were injected into C57BL/6 or BALB/c-nu/nu mice to establish lung metastasis...
April 1, 2018: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/29660160/digital-image-analysis-improves-precision-of-programmed-death-ligand-1-pd-l1-scoring-in-cutaneous-melanoma
#3
Viktor H Koelzer, Aline Gisler, Jonathan C Hanhart, Johannes Griss, Stephan N Wagner, Niels Willi, Gieri Cathomas, Melanie Sachs, Werner Kempf, Daniela S Thommen, Kirsten D Mertz
AIMS: Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (PD-L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD-L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardized digital protocol for the assessment of PD-L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists...
April 16, 2018: Histopathology
https://www.readbyqxmd.com/read/29658430/adjuvant-pembrolizumab-versus-placebo-in-resected-stage-iii-melanoma
#4
Alexander M M Eggermont, Christian U Blank, Mario Mandala, Georgina V Long, Victoria Atkinson, Stéphane Dalle, Andrew Haydon, Mikhail Lichinitser, Adnan Khattak, Matteo S Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A Ascierto, Piotr Rutkowski, Dirk Schadendorf, Rutger Koornstra, Leonel Hernandez-Aya, Michele Maio, Alfonsus J M van den Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Paul Lorigan, Nageatte Ibrahim, Sandrine Marreaud, Alexander C J van Akkooi, Stefan Suciu, Caroline Robert
Background The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. Methods Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred...
April 15, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29657137/adjuvant-therapy-for-melanoma-prolongs-rfs
#5
(no author information available yet)
The PD-1 inhibitor pembrolizumab may be an effective adjuvant therapy for patients with stage III melanoma. In a clinical trial, patients who received the drug had a 12-month recurrence-free survival rate of 75.4%, compared with 61% for patients who received a placebo.
April 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29656892/cancer-germline-antigen-expression-discriminates-clinical-outcome-to-ctla-4-blockade
#6
Sachet A Shukla, Pavan Bachireddy, Bastian Schilling, Christina Galonska, Qian Zhan, Clyde Bango, Rupert Langer, Patrick C Lee, Daniel Gusenleitner, Derin B Keskin, Mehrtash Babadi, Arman Mohammad, Andreas Gnirke, Kendell Clement, Zachary J Cartun, Eliezer M Van Allen, Diana Miao, Ying Huang, Alexandra Snyder, Taha Merghoub, Jedd D Wolchok, Levi A Garraway, Alexander Meissner, Jeffrey S Weber, Nir Hacohen, Donna Neuberg, Patrick R Potts, George F Murphy, Christine G Lian, Dirk Schadendorf, F Stephen Hodi, Catherine J Wu
CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro...
April 6, 2018: Cell
https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#7
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29656235/effective-cancer-immunotherapy-in-mice-by-polyic-imiquimod-complexes-and-engineered-magnetic-nanoparticles
#8
Ana Isabel Bocanegra Gondan, Ane Ruiz-de-Angulo, Aintzane Zabaleta, Nina Gómez Blanco, Beatriz Macarena Cobaleda-Siles, María Jesús García-Granda, Daniel Padro, Jordi Llop, Blanca Arnaiz, María Gato, David Escors, Juan C Mareque-Rivas
Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs)...
April 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29644214/anti-pd-1-and-anti-ctla-4-therapies-in-cancer-mechanisms-of-action-efficacy-and-limitations
#9
REVIEW
Judith A Seidel, Atsushi Otsuka, Kenji Kabashima
Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29643991/serum-levels-of-soluble-cd163-and-cxcl5-may-be-predictive-markers-for-immune-related-adverse-events-in-patients-with-advanced-melanoma-treated-with-nivolumab-a-pilot-study
#10
Taku Fujimura, Yota Sato, Kayo Tanita, Yumi Kambayashi, Atsushi Otsuka, Yasuhiro Fujisawa, Koji Yoshino, Shigeto Matsushita, Takeru Funakoshi, Hiroo Hata, Yuki Yamamoto, Hiroshi Uchi, Yumi Nonomura, Ryota Tanaka, Megumi Aoki, Keisuke Imafuku, Hisako Okuhira, Sadanori Furudate, Takanori Hidaka, Setsuya Aiba
Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in the treatment of various cancers including advanced melanoma. The anti-PD-1 Ab significantly prolongs survival in patients with metastatic melanoma, and its administration in combination with local or systemic therapy may also lead to improved outcomes. Although anti-PD-1 Ab-based combined therapy might be effective for the treatment of advanced melanoma, the associated risk of irAEs is an important consideration. Therefore, being able to predict irAEs is of great interest to oncologists...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29628796/immunotherapy-of-melanoma
#11
Iwona Lugowska, Pawel Teterycz, Piotr Rutkowski
The immunotherapy is currently changing the landscape of oncology. Nowadays the standard of care in metastatic or unresectable melanoma patients include immunomodulating modalities such as anti-PD-1 drugs (nivolumab, pembrolizumab) and anti-CTLA-4 antibody ipilimumab. The improvements of progression free survival and overall survival connected with those treatments were unprecedented and have been confirmed in stage III trials. The efficacy of immunotherapy in metastatic setting can be further upgraded in some groups of patients by combining both types of antibodies...
March 2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29623227/fulminant-diabetes-in-a-patient-with-advanced-melanoma-on-nivolumab
#12
Nora Chokr, Hafsa Farooq, Elizabeth Guadalupe
Background: Anti-PD-1 agents were approved for advanced melanoma after the landmark trial Checkmate-037. Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells in genetically predisposed people. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy. Case: A 61-year-old male with advanced melanoma presented with a three-day history of nausea, vomiting, and malaise...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29622046/complete-intracranial-response-to-talimogene-laherparepvec-t-vec-pembrolizumab-and-whole-brain-radiotherapy-in-a-patient-with-melanoma-brain-metastases-refractory-to-dual-checkpoint-inhibition
#13
Zoë Blake, Douglas K Marks, Robyn D Gartrell, Thomas Hart, Patti Horton, Simon K Cheng, Bret Taback, Basil A Horst, Yvonne M Saenger
BACKGROUND: Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. CASE PRESENTATION: We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases...
April 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29619980/targeting-myeloid-derived-suppressor-cells-and-programmed-death-ligand-1-confers-therapeutic-advantage-of-ablative-hypofractionated-radiation-therapy-compared-with-conventional-fractionated-radiation-therapy
#14
Jie Lan, Rui Li, Li-Mei Yin, Lei Deng, Jun Gui, Bao-Qing Chen, Lin Zhou, Mao-Bin Meng, Qiao-Rong Huang, Xian-Ming Mo, Yu-Quan Wei, Bo Lu, Adam Dicker, Jian-Xin Xue, You Lu
PURPOSE: Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT. METHODS AND MATERIALS: We established subcutaneous tumors using syngeneic lung cancer and melanoma cells in both immunocompetent and immunocompromised mice and treated them with AHFRT and CFRT under the same biologically equivalent dose...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29619406/unique-cytologic-features-of-thyroiditis-caused-by-immune-checkpoint-inhibitor-therapy-for-malignant-melanoma
#15
Trevor E Angell, Le Min, Tad J Wieczorek, F Stephen Hodi
Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer patients. Monoclonal antibodies targeting two such molecules, Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) have shown clinical benefit in the treatment of advanced malignancies, including metastatic melanoma. Adverse effects of these immune checkpoint inhibitors include immune-related adverse events (irAE) and the inducing of new autoimmunity, of which one of the most common is autoimmune thyroiditis...
March 2018: Genes & Diseases
https://www.readbyqxmd.com/read/29617862/generation-of-tumor-antigen-specific-murine-cd8-t-cells-with-enhanced-anti-tumor-activity-via-highly-efficient-crispr-cas9-genome-editing
#16
Yasuo Ouchi, Ashwini Patil, Yusuke Tamura, Hiroshi Nishimasu, Aina Negishi, Sudip Kumar Paul, Naoki Takemura, Takeshi Satoh, Yasumasa Kimura, Makoto Kurachi, Osamu Nureki, Kenta Nakai, Hiroshi Kiyono, Satoshi Uematsu
Immunotherapies have led to the successful development of novel therapies for cancer. However, there is increasing concern regarding the adverse effects caused by non-tumor-specific immune responses. Here, we report an effective strategy to generate high-avidity tumor-antigen-specific CTLs, using Cas9/single-guide RNA (sgRNA) ribonucleoprotein (RNP) delivery. As a proof-of-principle demonstration, we selected the gp100 melanoma-associated tumor antigen, and cloned the gp100-specific high-avidity TCR from gp100-immunized mice...
April 3, 2018: International Immunology
https://www.readbyqxmd.com/read/29616914/association-of-inflammatory-markers-with-disease-progression-in-patients-with-metastatic-melanoma-treated-with-immune-checkpoint-inhibitors
#17
Minggui Pan, Mubarika Alavi, Lisa J Herrinton
INTRODUCTION: We investigated the effect of inflammatory biomarkers (neutrophil, platelet, and lymphocyte counts) on risk of progression in patients with metastatic melanoma treated with an immune checkpoint inhibitor targeting programmed cell death protein-1 (PD-1). METHODS: This retrospective cohort study included 108 patients with malignant melanoma treated with an anti-PD-1 checkpoint inhibitor from August 2014 through December 2015. The outcome was disease progression noted on imaging or clinical examination...
March 30, 2018: Permanente Journal
https://www.readbyqxmd.com/read/29610684/immune-toxicity-with-checkpoint-inhibition-for-metastatic-melanoma-case-series-and-clinical-management
#18
Anna J Lomax, Jennifer Lim, Robert Cheng, Arianne Sweeting, Patricia Lowe, Neil McGill, Nicholas Shackel, Elizabeth L Chua, Catriona McNeil
Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab)...
2018: Journal of Skin Cancer
https://www.readbyqxmd.com/read/29608408/monoclonal-antibody-l-1-mab-13-detected-human-pd-l1-in-lung-cancers
#19
Shinji Yamada, Shunsuke Itai, Takuro Nakamura, Miyuki Yanaka, Yao-Wen Chang, Hiroyoshi Suzuki, Mika K Kaneko, Yukinari Kato
Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L1 Mab-13 (IgG1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses...
April 2, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29607663/optimal-evaluation-of-programmed-death-ligand-1-on-tumor-cells-versus-immune-cells-requires-different-detection-methods
#20
Kelly A Schats, Emily A Van Vré, Carolien Boeckx, Martine De Bie, Dorien M Schrijvers, Bart Neyns, Ingrid De Meester, Mark M Kockx
CONTEXT: - The benefit of programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) as a method to select patients who may benefit from programmed death receptor-1 (PD-1)/PD-L1 immunotherapies remains uncertain in many tumor indications. OBJECTIVES: - To compare the commercially available, approved PD-L1 IHC assays (22C3, 28-8, SP142, SP263), specifically identifying the changes in staining output created by altering the detection method. DESIGN: - This pilot study investigates the respective PD-L1 kit assay staining patterns and related scoring of tumor cells and immune cells on lung carcinoma and melanoma...
April 2, 2018: Archives of Pathology & Laboratory Medicine
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