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Burak Bilgin, Mehmet A N Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aim to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in published or reported recent studies. SCOPE: A literature search was made from PubMed and ASCO Annual Meeting abstracts by using the following search keywords: "nivolumab", "pembrolizumab", "avelumab", "GI cancers" "anti-PD1 therapy" and "anti-PD-L1 therapy"...
January 31, 2017: Current Medical Research and Opinion
Filippo De Marinis, Antonio Passaro
The treatment of non-small cell lung cancer (NSCLC) is changing dramatically in the last period, considering both non-squamous and squamous disease. In the last five years, the identification of different molecular predictive biomarker (e.g., EGFR, ALK e ROS1) and the utilize of new chemotherapy agents associated or not with antiangiogenics agents (e.g., bevacizumab and nintedanib), allowed the improvement of survival and related responses to these treatments. However, these advances, did not allow an improvement of the same endpoints in the management of NSCLC with squamous cell histology (SCC), where until very recently, docetaxel in monotherapy remained as a corner stone treatment for the second line, although associated with an unfavorable toxicity profile...
December 2016: Recenti Progressi in Medicina
H Kaufman, M Kraemer, C Dias Barbosa, J Lambert, L Mahnke, M Bharmal
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
Janice M Reichert
Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6-9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US...
February 2017: MAbs
Amruth R Palla, Devin Kennedy, Hossain Mosharraf, Donald Doll
Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al...
September 2016: Case Reports in Oncology
Shuguang Tan, Danqing Chen, Kefang Liu, Mengnan He, Hao Song, Yi Shi, Jun Liu, Catherine W-H Zhang, Jianxun Qi, Jinghua Yan, Shan Gao, George F Gao
Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized...
December 2016: Protein & Cell
Tadanobu Nagaya, Yuko Nakamura, Kazuhide Sato, Toshiko Harada, Peter L Choyke, James W Hodge, Jeffrey Schlom, Hisataka Kobayashi
Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Programmed cell death protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb), avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441 cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR in vitro...
January 31, 2017: Oncotarget
Peter Sidaway
No abstract text is available yet for this article.
September 27, 2016: Nature Reviews. Clinical Oncology
Howard L Kaufman, Jeffery Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P D'Angelo, Kent C Shih, Céleste Lebbé, Gerald P Linette, Michele Milella, Isaac Brownell, Karl D Lewis, Jochen H Lorch, Kevin Chin, Lisa Mahnke, Anja von Heydebreck, Jean-Marie Cuillerot, Paul Nghiem
BACKGROUND: Merkel cell carcinoma is a rare, aggressive skin cancer with poor prognosis in patients with advanced disease. Current standard care uses various cytotoxic chemotherapy regimens, but responses are seldom durable. Tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, providing rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. We assessed treatment with avelumab, an anti-PD-L1 monoclonal antibody, in patients with stage IV Merkel cell carcinoma that had progressed after cytotoxic chemotherapy...
October 2016: Lancet Oncology
Kefang Liu, Shuguang Tan, Yan Chai, Danqing Chen, Hao Song, Catherine Wei-Hong Zhang, Yi Shi, Jun Liu, Wenjie Tan, Jianxin Lyu, Shan Gao, Jinghua Yan, Jianxun Qi, George F Gao
No abstract text is available yet for this article.
January 2017: Cell Research
Swati Khanna, Anish Thomas, Daniel Abate-Daga, Jingli Zhang, Betsy Morrow, Seth M Steinberg, Augusto Orlandi, Patrizia Ferroni, Jeffrey Schlom, Fiorella Guadagni, Raffit Hassan
INTRODUCTION: The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS: Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells...
November 2016: Journal of Thoracic Oncology
Amanda L Gill, Samantha A Green, Shahed Abdullah, Cecile Le Saout, Stefania Pittaluga, Hui Chen, Refika Turnier, Jeffrey Lifson, Steven Godin, Jing Qin, Michael C Sneller, Jean-Marie Cuillerot, Helen Sabzevari, H Clifford Lane, Marta Catalfamo
OBJECTIVE: The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target...
October 23, 2016: AIDS
Italia Grenga, Renee N Donahue, Lauren M Lepone, Jacob Richards, Jeffrey Schlom
Monoclonal antibodies (MAbs) that interfere with checkpoint molecules are being investigated for the treatment of infectious diseases and cancer, with the aim of enhancing the function of an impaired immune system. Avelumab (MSB0010718C) is a fully human IgG1 MAb targeting programmed death-ligand 1 (PD-L1), which differs from other checkpoint-blocking antibodies in its ability to mediate antibody-dependent cell-mediated cytotoxicity. These studies were conducted to define whether avelumab could enhance the detection of antigen-specific immune response in in vitro assays...
May 2016: Clinical & Translational Immunology
Ian A Cree, Richard Booton, Paul Cane, John Gosney, Merdol Ibrahim, Keith Kerr, Rohit Lal, Conrad Lewanski, Neal Navani, Andrew G Nicholson, Marianne Nicolson, Yvonne Summers
A new approach to the management of non-small-cell lung cancer (NSCLC) has recently emerged that works by manipulating the immune checkpoint controlled by programmed death receptor 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Several drugs targeting PD-1 (pembrolizumab and nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved or are in the late stages of development. Inevitably, the introduction of these drugs will put pressure on healthcare systems, and there is a need to stratify patients to identify those who are most likely to benefit from such treatment...
August 2016: Histopathology
Rika Fujii, Eitan R Friedman, Jacob Richards, Kwong Y Tsang, Christopher R Heery, Jeffrey Schlom, James W Hodge
Chordoma, a rare bone tumor derived from the notochord, has been shown to be resistant to conventional therapies. Checkpoint inhibition has shown great promise in immune-mediated therapy of diverse cancers. The anti-PD-L1 mAb avelumab is unique among checkpoint inhibitors in that it is a fully human IgG1 capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) of PD-L1-expressing tumor cells. Here, we investigated avelumab as a potential therapy for chordoma. We examined 4 chordoma cell lines, first for expression of PD-L1, and in vitro for ADCC killing using NK cells and avelumab...
June 7, 2016: Oncotarget
Amanda J Vandeveer, Jonathan K Fallon, Robert Tighe, Helen Sabzevari, Jeffrey Schlom, John W Greiner
Bacillus Calmette-Guerin (BCG) is the standard of care for intravesical therapy for carcinoma in situ and non-muscle invasive, nonmetastatic human urothelial carcinoma. Although the responsiveness to this immunotherapeutic is believed to be linked with (i) a high number of somatic mutations and (ii) a large number of tumor-infiltrating lymphocytes, recent findings of the roles that inhibitory immune receptors and their ligands play in tumor evasion may provide insights into the limitations of the effectiveness of BCG and offer new targets for immune-based therapy...
2016: Cancer Immunology Research
Maria Alsina, Markus Moehler, Cinta Hierro, Raquel Guardeño, Josep Tabernero
Gastric cancer (GC) is a major world-wide health problem. It is the third leading cause of death from cancer. The treatment of advanced GC by chemotherapy has limited efficacy. The addition of some targeted therapies like trastuzumab and ramucirumab have added a modest benefit, but only in human epidermal growth factor receptor 2 (ERBB2 or HER2)-positive patients and in the second-line setting, respectively. The development of new and effective therapeutic strategies must consider the genetic complexity and heterogeneity of GC; prognostic and predictive biomarkers should be identified for clinical implementation...
August 2016: Targeted Oncology
Benjamin Boyerinas, Caroline Jochems, Massimo Fantini, Christopher R Heery, James L Gulley, Kwong Yok Tsang, Jeffrey Schlom
Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells...
October 2015: Cancer Immunology Research
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