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https://www.readbyqxmd.com/read/28334399/association-of-hiv-status-with-local-immune-response-to-anal-squamous-cell-carcinoma-implications-for-immunotherapy
#1
Elizabeth L Yanik, Genevieve J Kaunitz, Tricia R Cottrell, Farah Succaria, Tracee L McMiller, Maria L Ascierto, Jessica Esandrio, Haiying Xu, Aleksandra Ogurtsova, Toby Cornish, Evan J Lipson, Suzanne L Topalian, Eric A Engels, Janis M Taube
Importance: The programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway play an important immunosuppressive role in cancer and chronic viral infection, and have been effectively targeted in cancer therapy. Anal squamous cell carcinoma (SCC) is associated with both human papillomavirus and HIV infection. To date, patients with HIV have been excluded from most trials of immune checkpoint blocking agents, such as anti-PD-1 and anti-PD-L1, because it was assumed that their antitumor immunity was compromised compared with immunocompetent patients...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28331615/nuclear-irf-1-expression-as-a-mechanism-to-assess-capability-to-express-pd-l1-and-response-to-pd-1-therapy-in-metastatic-melanoma
#2
James W Smithy, Lauren M Moore, Vasiliki Pelekanou, Jamaal Rehman, Patricia Gaule, Pok Fai Wong, Veronique M Neumeister, Mario Sznol, Harriet M Kluger, David L Rimm
BACKGROUND: Predictive biomarkers for antibodies against programmed death 1 (PD-1) remain a major unmet need in metastatic melanoma. Specifically, response is seen in tumors that do not express programmed death ligand 1 (PD-L1), highlighting the need for a more sensitive biomarker. We hypothesize that capacity to express PD-L1, as assessed by an assay for a PD-L1 transcription factor, interferon regulatory factor 1 (IRF-1), may better distinguish patients likely to benefit from anti-PD-1 immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28325255/mucosal-melanoma-of-the-head-and-neck
#3
REVIEW
Paolo Antonio Ascierto, Remo Accorona, Gerardo Botti, Davide Farina, Piero Fossati, Gemma Gatta, Helen Gogas, Davide Lombardi, Roberto Maroldi, Piero Nicolai, Marco Ravanelli, Vito Vanella
Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28324889/evaluation-of-clinicopathological-factors-in-pd-1-response-derivation-and-validation-of-a-prediction-scale-for-response-to-pd-1-monotherapy
#4
Adi Nosrati, Katy K Tsai, Simone M Goldinger, Paul Tumeh, Barbara Grimes, Kimberly Loo, Alain P Algazi, Thi Dan Linh Nguyen-Kim, Mitchell Levesque, Reinhard Dummer, Omid Hamid, Adil Daud
BACKGROUND: Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy. METHODS: A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg(-1) Q2W or Q3W) or nivolumab (3 mg kg(-1) Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale...
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28324885/reply-to-comment-on-efficacy-and-toxicity-of-treatment-with-the-anti-ctla-4-antibody-ipilimumab-in-patients-with-metastatic-melanoma-after-prior-anti-pd-1-therapy
#5
Samantha Bowyer, Prashanth Prithviraj, Paul Lorigan, James Larkin, Grant McArthur, Victoria Atkinson, Michael Millward, Muoi Khou, Stefan Diem, Sangeetha Ramanujam, Ben Kong, Elizabeth Liniker, Alexander Guminski, Phillip Parente, Miles C Andrews, Sagun Parakh, Jonathan Cebon, Georgina V Long, Matteo S Carlino, Oliver Klein
No abstract text is available yet for this article.
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28324884/comment-on-efficacy-and-toxicity-of-treatment-with-the-anti-ctla-4-antibody-ipilimumab-in-patients-with-metastatic-melanoma-after-prior-anti-pd-1-therapy
#6
Keisuke Imafuku, Koji Yoshino, Kei Yamaguchi, Satoshi Tsuboi, Kuniaki Ohara, Hiroo Hata
No abstract text is available yet for this article.
March 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#7
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28322160/an-efficient-transient-expression-system-for-enhancing-generation-of-monoclonal-antibodies-in-293-suspension-cells
#8
Guoquan Zhang, Jie Liu, Wanting Fan, Qianyi Chen, Bin Shi
BACKGROUND: Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAb in mammalian cells. However, though a few commercial expression systems of mAbs can be listened, the high expense often impedes academia researches. METHODS: In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contains internal ribosome entry site (IRES) and enhancer elements to express IgG1 light chain (LC) and heavy chain (HC) in one transcript...
March 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28321814/immunotherapy-in-nsclc-a-promising-and-revolutionary-weapon
#9
Christian Rolfo, Christian Caglevic, Mariacarmela Santarpia, Antonio Araujo, Elisa Giovannetti, Carolina Diaz Gallardo, Patrick Pauwels, Mauricio Mahave
Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28320090/treatment-with-anti-programmed-cell-death-1-pd-1-antibody-restored-postoperative-cd8-t-cell-dysfunction-by-surgical-stress
#10
Zhirong Sun, Anrong Mao, Yun Wang, Yanjun Zhao, Jiawei Chen, Pingbo Xu, Changhong Miao
Millions of patients benefit from surgery and are exposed to surgical stress. However, ample studies suggest that surgical stress contributes to tumor recurrence or distant metastases. Surgical stress suppresses CD8+ T cells (CTL) function which is vital for eliminating the malignant cells. Anti-programmed cell death 1 (PD-1) therapy is an effective and safe treatment that increases survival rate of patients with multiple cancers, however, whether anti-PD-1 therapy is able to reverse the immunosuppression following surgery remains largely unknown...
March 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28318951/a-comprehensive-analysis-of-programmed-cell-death-ligand-1-expression-with-the-clone-sp142-antibody-in-non-small-cell-lung-cancer%C3%A2-patients
#11
Kazuki Takada, Gouji Toyokawa, Tatsuro Okamoto, Mototsugu Shimokawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Fumihiro Shoji, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with anti-PD-1 therapy currently the standard treatment for non-small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC...
March 2, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28314298/multi-omics-profiling-of-patients-with-melanoma-treated-with-nivolumab-in-project-hope
#12
Shusuke Yoshikawa, Yoshio Kiyohara, Masaki Otsuka, Ryota Kondou, Chizu Nonomura, Haruo Miyata, Akira Iizuka, Keiichi Ohshima, Kenichi Urakami, Takeshi Nagashima, Masatoshi Kusuhara, Takashi Sugino, Tohru Mochizuki, Ken Yamaguchi, Yasuto Akiyama
BACKGROUND: Project HOPE (High-tech Omics-based Patient Evaluation) has been in progress since 2014 and uses whole-exome sequencing (WES) and gene expression profiling (GEP). Among a total of 1,685 patients with cancer, 13 with melanoma were registered and characterized using multi-omics analyses to investigate specific biomarkers in responders to programmed cell death-1 (PD-1) blockade. MATERIALS AND METHODS: The patients with melanoma comprised of six males and seven females, and their mean age was 68 years...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28302866/genomic-profiling-of-patient-derived-xenografts-for-lung-cancer-identifies-b2m-inactivation-impairing-immunorecognition
#13
Carolina Pereira, Pol Gimenez-Xavier, Eva Pros, Maria J Pajares, Massimo Moro, Antonio Gomez, Alejandro Navarro, Enric Condom, Sebastian Moran, Gonzalo Gomez-Lopez, Osvaldo Graña, Miriam Rubio-Camarillo, Alex Martinez-Martí, Jun Yokota, Julian Carretero, Jose M Galbis, Ernest Nadal, David Pisano, Gabriella Sozzi, Enriqueta Felip, Luis M Montuenga, Luca Roz, Alberto Villanueva, Montse Sanchez-Cespedes
Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs).Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex.Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers...
March 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28300475/epitope-mapping-reveals-the-binding-mechanism-of-a-functional-antibody-cross-reactive-to-both-human-and-murine-programmed-death-1
#14
Dong Li, Jianqing Xu, Zhuozhi Wang, Zhen Gong, Jieying Liu, Yong Zheng, Jian Li, Jing Li
Of the inhibitory checkpoints in the immune system, programmed death 1 (PD-1) is one of the most promising targets for cancer immunotherapy. The anti-PD-1 antibodies currently approved for clinical use or under development bind to human PD-1 (hPD-1), but not murine PD-1. To facilitate studies in murine models, we developed a functional antibody against both human and murine PD-1, and compared the epitopes of such antibody to a counterpart that only bound to hPD-1. To quickly identify the epitopes of the 2 antibodies, we used alanine scanning and mammalian cell expression cassette...
February 23, 2017: MAbs
https://www.readbyqxmd.com/read/28296676/histopathologic-features-of-colitis-due-to-immunotherapy-with-anti-pd-1-antibodies
#15
Jonathan H Chen, Maryam K Pezhouh, Gregory Y Lauwers, Ricard Masia
Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28295707/anti-pd-1-pd-l1-induced-psoriasis-from-an-oncological-perspective
#16
Juan Ruiz-Bañobre, Jorge García-González
We read with interest the letter to the editor by Bonigen et al(1) regarding the development of psoriasis during anti-programed cell death protein 1 (PD-1) therapy. The authors describe a series of 17 patients diagnosed with melanoma or lung cancer treated with anti-PD-1 drugs in first line or later. In the final analysis, they also include 4 patients previously described in the literature. This article is protected by copyright. All rights reserved.
March 10, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28292987/-management-of-toxicities-of-immune-checkpoint-inhibitors
#17
Yoshitsugu Horio
Immune checkpoint inhibitors, including the anti-CTLA-4 antibody ipilimumab, the anti-PD-1 antibodies nivolumab and pembrolizumab, and the anti-PD-L1 antibody atezolizumab had produced long-lasting tumor responses in several malignancies. Immune-related Adverse Events(irAEs)which are different from adverse events of conventional chemotherapy and molecular targeted therapy, occur as a consequence of impaired self-tolerance from loss of T-cell inhibition. The main irAEs of immune checkpoint inhibitors include dermatological, gastrointestinal, pulmonary, hepatic, endocrine, renal toxicities...
March 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28288993/a-combined-pd-1-c5a-blockade-synergistically-protects-against-lung-cancer-growth-and-metastasis
#18
Daniel Ajona, Sergio Ortiz-Espinosa, Haritz Moreno, Teresa Lozano, Maria J Pajares, Jackeline Agorreta, Cristina Bértolo, Juan J Lasarte, Silvestre Vicent, Axel Vater, Fernando Lecanda, Luis M Montuenga, Ruben Pio
Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that a combined inhibition of C5a/C5aR1 and PD-1 signaling may have an antitumor synergistic effect. RMP1-14 antibody was used to block PD-1 and an L-aptamer to inhibit signaling of complement C5a with its receptors. Using syngeneic models of lung cancer we demonstrate that the combination of C5a and PD-1 blockade markedly reduces tumor growth and metastasis, and leads to prolonged survival...
March 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28286532/efficacy-of-juzentaihoto-for-tumor-immunotherapy-in-b16-melanoma-metastasis-model
#19
Shintaro Ishikawa, Takako Ishikawa, Chiaki Tezuka, Kazuhito Asano, Masataka Sunagawa, Tadashi Hisamitsu
Introduction. Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence. In this study, we examined the effects of JTT on natural killer (NK) cell activity and metastasis in combined treatments with anti-PD-1 antibody in a mouse model of melanoma metastasis. Methods. C57BL/6 male mice were intravenously injected with B16 melanoma cells (B16 cell) and were given chow containing 3% JTT. In subsequent in vivo experiments, we assessed serum cytokine levels and tumor colony formation in the lungs...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28283736/phase-1b-study-of-pembrolizumab-mk-3475-anti-pd-1-monoclonal-antibody-in-japanese-patients-with-advanced-melanoma-keynote-041
#20
Naoya Yamazaki, Tatsuya Takenouchi, Manabu Fujimoto, Hironobu Ihn, Hiroshi Uchi, Takashi Inozume, Yoshio Kiyohara, Hisashi Uhara, Kazuhiko Nakagawa, Hiroshi Furukawa, Hidefumi Wada, Kazuo Noguchi, Takashi Shimamoto, Kenji Yokota
PURPOSE: This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. METHODS: Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review. RESULTS: Forty-two patients with advanced melanoma received pembrolizumab...
March 11, 2017: Cancer Chemotherapy and Pharmacology
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