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https://www.readbyqxmd.com/read/28529897/uncovering-the-immune-tumor-microenvironment-in-non-small-cell-lung-cancer-to-understand-response-rates-to-checkpoint-blockade-and-radiation
#1
REVIEW
Jonathan E Schoenhals, Steven N Seyedin, Clark Anderson, Eric D Brooks, Yun R Li, Ahmed I Younes, Sharareh Niknam, Ailin Li, Hampartsoum B Barsoumian, Maria Angelica Cortez, James W Welsh
The study of immunology has led to breakthroughs in treating non-small cell lung cancer (NSCLC). The recent approval of an anti-PD1 checkpoint drug for NSCLC has generated much interest in novel combination therapies that might provide further benefit for patients. However, a better understanding of which combinations may (or may not) work in NSCLC requires understanding the lung immune microenvironment under homeostatic conditions and the changes in that microenvironment in the setting of cancer progression and with radiotherapy...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28524161/efficacy-of-anti-pd-1-therapy-in-patients-with-melanoma-brain-metastases
#2
Sagun Parakh, John J Park, Shehara Mendis, Rajat Rai, Wen Xu, Serigne Lo, Martin Drummond, Catherine Rowe, Annie Wong, Grant McArthur, Andrew Haydon, Miles C Andrews, Jonathan Cebon, Alex Guminski, Richard F Kefford, Georgina V Long, Alexander M Menzies, Oliver Klein, Matteo S Carlino
BACKGROUND: There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic. METHOD: We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions used to determine IC response, disease control rate (DCR) and progression-free survival (PFS)...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28523098/incb24360-epacadostat-a-highly-potent-and-selective-indoleamine-2-3-dioxygenase-1-ido1-inhibitor-for-immuno-oncology
#3
Eddy W Yue, Richard Sparks, Padmaja Polam, Dilip Modi, Brent Douty, Brian Wayland, Brian Glass, Amy Takvorian, Joseph Glenn, Wenyu Zhu, Michael Bower, Xiangdong Liu, Lynn Leffet, Qian Wang, Kevin J Bowman, Michael J Hansbury, Min Wei, Yanlong Li, Richard Wynn, Timothy C Burn, Holly K Koblish, Jordan S Fridman, Tom Emm, Peggy A Scherle, Brian Metcalf, Andrew P Combs
A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 4f, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#4
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28511378/cortical-potentials-prior-to-movement-in-parkinson-s-disease
#5
Ashlesh Laxman Patil, Sanjay Kumar Sood, Vinay Goyal, Kanwal Preet Kochhar
INTRODUCTION: Recording cortical potentials prior to movement (bereitschaftspotentials, BP) offer a good non invasive method for studying activity of motor related cortices in Parkinson's Disease (PD). Dopaminergic medications provide some symptomatic relief in advanced stages but they do not stop the progression of the disease. Assessing BP may be a good idea to see the response of anti PD drugs. It remains unclear whether the anti PD medications also improve cortical activity prior to movement even in advanced stages of the disease...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#6
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28505010/tackling-immunomonitoring-in-gastrointestinal-cancer
#7
Maëlle Anciaux, Caroline Vandeputte, Alain Hendlisz
PURPOSE OF REVIEW: The growing awareness that the immune system is a key player in the antitumoral response and the excellent clinical results achieved in some settings with anti-programmed cell death 1 (PD1)/programmed death ligand 1 (PDL1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) drugs has led to the rise of immunotherapy as a supplement or an alternative to conventional cancer treatment. The high costs associated with these therapies, their significant toxicity and the need to understand and circumvent immune escape mechanisms raise the urgent need for immunological assessment of therapy response...
May 12, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28492495/immunotherapy-for-colorectal-cancer
#8
REVIEW
Patrick M Boland, Wen Wee Ma
The recent success of anti-PD1 drugs in metastatic colorectal cancer patients with mismatch repair deficiency generated overwhelming enthusiasm for immunotherapy in the disease. However, patients with mismatch repair deficient colorectal cancer represent only a small subset of the metastatic population. Current research focuses on advancing immunotherapy to earlier stages of the disease including adjuvant and first-line metastatic settings, and on inducing sensitivity to immune checkpoint inhibitor therapy through a combinatorial approach...
May 11, 2017: Cancers
https://www.readbyqxmd.com/read/28491135/highlights-from-the-15th-st-gallen-international-breast-cancer-conference-15-18-march-2017-vienna-tailored-treatments-for-patients-with-early-breast-cancer
#9
Consuelo Morigi
The 15th St Gallen International Breast Cancer Conference was held in Vienna for the second time, from 15th-18th March 2017. 4000 people from 105 countries all over the world were invited to take part in the event. The real highlight of the conference was the last day with the International Consensus Session which was chaired by around 50 experts on breast cancer worldwide. With reference to data from scientific research, the consensus panel tried to offer guidelines for the management of breast cancer with the aim of providing patients with optimal treatment...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28487385/immune-related-gene-expression-profiling-after-pd-1-blockade-in-non-small-cell-lung-carcinoma-head-and-neck-squamous-cell-carcinoma-and-melanoma
#10
Aleix Prat, Alejandro Navarro, Laia Paré, Noemí Reguart, Patricia Galvan, Tomás Pascual, Alex Martínez, Paolo Nuciforo, Laura Comerma, Llucia Alos, Nuria Pardo, Susana Cedrés, Cheng Fan, Joel S Parker, Lydia Gaba, Ivan Victoria, Nuria Viñolas, Ana Vivancos, Ana Arance, Enriqueta Felip
Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor speciments from 65 patients with melanoma, lung non-squamous, squamous cell lung or head and neck cancers who were treated with the approved PD1 targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS)...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28480062/locoregional-and-systemic-therapy-for-hepatocellular-carcinoma
#11
REVIEW
Olumide B Gbolahan, Michael A Schacht, Eric W Beckley, Thomas P LaRoche, Bert H O'Neil, Maximilian Pyko
The management of hepatocellular carcinoma (HCC) remains challenging due to late presentation and the presence of accompanying liver dysfunction. As such, most patients are not eligible for curative resection and liver transplant. Management in this scenario depends on a number of factors including hepatic function, tumor burden, patency of hepatic vasculature and patients' functional status. Based on these, patients can be offered catheter based intra-arterial therapy for intermediate stage disease and in more advanced disease, sorafenib...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28476944/impact-of-age-on-outcomes-with-immunotherapy-for-patients-with-melanoma
#12
Allison S Betof, Ryan D Nipp, Anita Giobbie-Hurder, Romany A N Johnpulle, Krista Rubin, Samuel M Rubinstein, Keith T Flaherty, Donald P Lawrence, Douglas B Johnson, Ryan J Sullivan
BACKGROUND: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers. METHODS: We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015...
May 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28459943/circulating-tumor-dna-changes-for-early-monitoring-of-anti-pd1-immunotherapy-a-proof-of-concept-study
#13
L Cabel, F Riva, V Servois, A Livartowski, C Daniel, A Rampanou, O Lantz, E Romano, M Milder, B Buecher, S Piperno-Neumann, V Bernard, S Baulande, I Bieche, J Y Pierga, C Proudhon, F C Bidard
BackgroundRecent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab, pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.Patients and methodsThis prospective pilot study was conducted in patients with non-small cell lung cancer, uveal melanoma or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie...
April 29, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28438383/remitting-seronegative-symmetrical-synovitis-with-pitting-edema-rs3pe-syndrome-induced-by-nivolumab
#14
Marie-Léa Gauci, Barouyr Baroudjian, Pauline Laly, Isabelle Madelaine, Laetitia Da Meda, Laetitia Vercellino, Martine Bagot, Frédéric Lioté, Cécile Pages, Céleste Lebbé
INTRODUCTION: A new articular syndrome described as immunrelated side effect of immunotherapy: PD-1 inhibitors have revolutionized the treatment of advanced melanoma but are responsible for immune-related toxicity. We report a case of remitting seronegative symetrical synovitis with pitting edema (RS3PE) syndrome induced by nivolumab. CASE REPORT: A 80 year-old man with stage IV BRAF-wild type and NRAS exon 2-mutated melanoma was treated first line by nivolumab 3mg/kg every 2 weeks...
March 8, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#15
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/28434398/the-use-of-immunotherapy-in-the-treatment-of-melanoma
#16
REVIEW
Tala Achkar, Ahmad A Tarhini
Patients with advanced melanoma have a compromised anti-tumor immune response leading to tumor immune tolerance and a tumor microenvironment conducive to disease progression. Immunotherapy that successfully overcomes this tumor-mediated immune suppression has made the greatest impact in the management of this disease over the past few years. This progress through immunotherapy builds upon earlier successes that interferon-α had in the treatment of melanoma in the adjuvant setting, as well as that of high-dose interleukin-2 in advanced melanoma...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28431490/new-challenges-in-therapeutic-vaccines-against-hiv-infection
#17
Lorna Leal, Constanza Lucero, Josep M Gatell, Teresa Gallart, Montserrat Plana, Felipe García
There is a growing interest in developing curative strategies for HIV infection. Therapeutic vaccines are one of the most promising approaches. We will review the current knowledge and the new challenges in this research field. Areas covered: PubMed and ClinicalTrial.gov databases were searched to review the progress and prospects for clinical development of immunotherapies aimed to cure HIV infection. Dendritic cells (DC)-based vaccines have yielded the best results in the field. However, major immune-virologic barriers may hamper current vaccine strategies...
May 4, 2017: Expert Review of Vaccines
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
#18
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/28414668/autoimmune-diabetes-presented-with-diabetic-ketoacidosis-induced-by-immunotherapy-in-an-adult-with-melanoma
#19
A A Alzenaidi, J Dendy, L Rejjal
INTRODUCTION: Immunotherapy has been approved for treatment of melanoma. Autoimmune endocrinopathies have been reported in trials involving immunotherapy but autoimmune diabetes has not been definitively linked to them. Here we describe a case of autoimmune diabetes presenting with DKA after receiving combined immunotherapy with anti-CTLA4 and anti-PD1 monoclonal antibodies. CASE: A 47year old gentleman with metastatic melanoma presented to our institution with confusion, abdominal pain and decreased oral intake...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28407528/immunotherapy-revolutionises-non-small-cell-lung-cancer-therapy-results-perspectives-and-new-challenges
#20
REVIEW
Etienne Giroux Leprieur, Coraline Dumenil, Catherine Julie, Violaine Giraud, Jennifer Dumoulin, Sylvie Labrune, Thierry Chinet
Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10...
June 2017: European Journal of Cancer
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