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"immune checkpoint inhibitor"

Tyler P Robin, Robert E Breeze, Derek E Smith, Chad G Rusthoven, Karl D Lewis, Rene Gonzalez, Amanda Brill, Robin Saiki, Kelly Stuhr, Laurie E Gaspar, Sana D Karam, David Raben, Brian D Kavanagh, Sameer K Nath, Arthur K Liu
INTRODUCTION: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. METHODS: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery...
June 16, 2018: Journal of Neuro-oncology
Megan B Barnet, Wendy A Cooper, Michael J Boyer, Steven Kao
Immune checkpoint inhibitors have shown efficacy in the treatment of non-small cell lung cancer (NSCLC) in the adjuvant, first- and subsequent-line settings. In metastatic disease, they provide hope of durable response where “best-case” scenario has long been inadequate. This progress has highlighted the immunogenic nature of NSCLC and invigorated research into immunotherapy in the field. In this review we consider the foundations of immunotherapy in NSCLC, canvass the current research and summarise the evidence guiding clinical practice...
June 14, 2018: Journal of Clinical Medicine
Alexander T Baker, Carmen Aguirre-Hernández, Gunnel Halldén, Alan L Parker
The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability...
June 14, 2018: Cancers
Ofrat Beyar-Katz, Saar Gill
Acute myeloid leukemia (AML) is a rapidly progressive, poor-prognosis malignancy arising from hematopoietic stem/progenitor cells. The long history of successful use of allogeneic hematopoietic cell transplantation (alloHCT) in AML indicates that this disease is immunoresponsive, leading to optimism that novel immunotherapies such as bispecific antibodies, chimeric antigen receptor T cells, and immune checkpoint inhibitors will generate meaningful disease control. However, emerging data on the immunoevasive tactics employed by AML blasts at diagnosis and at relapse indicate that optimism must be tempered by an understanding of this essential paradox...
June 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kinam Park
No abstract text is available yet for this article.
July 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Guoying Zhou, Lisanne Noordam, Dave Sprengers, Michail Doukas, Patrick P C Boor, Adriaan A van Beek, Remco Erkens, Shanta Mancham, Dirk Grünhagen, Anand G Menon, Johan F Lange, Pim J W A Burger, Alexandra Brandt, Boris Galjart, Cornelis Verhoef, Jaap Kwekkeboom, Marco J Bruno
Purpose : Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology : Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC...
2018: Oncoimmunology
Jieke Cui, Qing Li, Mei Luo, Zhaodong Zhong, Shu Zhou, Lin Jiang, Na Shen, Zhe Geng, Hui Cheng, Li Meng, Shujuan Yi, Hui Sun, Feifei Wu, Zunmin Zhu, Ping Zou, Yong You, An-Yuan Guo, Xiaojian Zhu
T cell function in cancer patients is usually impaired due to the constitutive activation of immune checkpoint inhibitors. This state is known as 'exhaustion' and is often associated with the inefficient control of tumors or persistent infections. In this work, we investigated the role of leukemia cell-derived microvesicles (MVs) in T cell exhaustion. Following incubation with MVs from various sources, all T cell subtypes exhibited the exhaustion phonotype and impaired cytokine secretion in vitro. Mice models also showed the connection between immune checkpoint inhibitors and MV injection...
2018: Oncoimmunology
Mareike Grees, Adi Sharbi-Yunger, Christos Evangelou, Daniel Baumann, Gal Cafri, Esther Tzehoval, Stefan B Eichmüller, Rienk Offringa, Jochen Utikal, Lea Eisenbach, Viktor Umansky
Despite melanoma immunogenicity and remarkable therapeutic effects of negative immune checkpoint inhibitors, a significant fraction of patients does not respond to current treatments. This could be due to limitations in tumor immunogenicity and profound immunosuppression in the melanoma microenvironment. Moreover, insufficient tumor antigen processing and presentation by dendritic cells (DC) may hamper the development of tumor-specific T cells. Using two genetically engineered mouse melanoma models ( RET and BRAFV600E transgenic mice), in which checkpoint inhibitor therapy alone is not efficacious, we performed proof-of-concept studies with an improved, multivalent DC vaccination strategy based on our recently developed genetic mRNA cancer vaccines...
2018: Oncoimmunology
Osama Mohamad, Alberto Diaz de Leon, Samuel Schroeder, Andrew Leiker, Alana Christie, Elizabeth Zhang-Velten, Lakshya Trivedi, Saad Khan, Neil B Desai, Aaron Laine, Kevin Albuquerque, Puneeth Iyengar, Yull Arriaga, Kevin Courtney, David E Gerber, Hans Hammers, Hak Choy, Robert Timmerman, James Brugarolas, Raquibul Hannan
Integration of hypofractionated body radiotherapy (H-RT) into immune checkpoint inhibitor (ICI) therapy may be a promising strategy to improve the outcomes of ICIs, although sufficient data is lacking regarding the safety and efficacy of this regimen. We, hereby, reviewed the safety and efficacy of this combination in 59 patients treated with H-RT during or within 8 weeks of ICI infusion and compared results with historical reports of ICI treatment alone. Most patients had RCC or melanoma. Median follow-up was 11 months...
2018: Oncoimmunology
Katharina C Kähler, Christine Blome, Andrea Forschner, Ralf Gutzmer, Axel Hauschild, Lucie Heinzerling, Elisabeth Livingstone, Carmen Loquai, Tina Müller-Brenne, Dirk Schadendorf, Jochen Utikal, Tobias Wagner, Matthias Augustin
After more than two decades with interferon alfa-2a and 2b (IFN) as the only approved drugs in the adjuvant setting for melanoma, new treatment approaches like immune checkpoint inhibitors and BRAF-MEK inhibitors improve the progression free survival (PFS) and also the overall survival (OS). We compared physicians' preferences ("utilities") for health states associated with IFN therapy to their patients' preferences. Utilities describe a preference for a specific health state on a scale of 0 (as bad as death) to 1...
May 25, 2018: Oncotarget
Matteo Santoni, Francesco Massari, Vincenzo Di Nunno, Alessandro Conti, Alessia Cimadamore, Marina Scarpelli, Rodolfo Montironi, Liang Cheng, Nicola Battelli, Antonio Lopez-Beltran
Advances in understanding the mechanisms of tumour-induced immunosuppression have led to the development of immune-checkpoint inhibitors in cancer patients, including those with renal cell carcinoma (RCC). The optimal combination between immunotherapy and targeted agents (as well as the possible favourable sequential therapy of these two classes of drugs) remains an open question at this moment. Several trials are currently underway to assess the combination of anti-programmed-death 1 (PD-1) or anti-PD-ligand(L)1 agents with other immunotherapies or with anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs)...
2018: Drugs in Context
Maria Saigi, Juan J Alburquerque-Bejar, Anne McLEER-Florin, Carolina Pereira, Eva Pros, Octavio A Romero, Nuria Baixeras, Anna Esteve-Codina, Ernest Nadal, Elisabeth Brambilla, Montse Sanchez-Cespedes
PURPOSE: The blockade of immune checkpoints such as PD-L1 and PD-1 is being exploited therapeutically in several types of malignancies. Here, we aimed to understand the contribution of the genetics of lung cancer (LC) to the ability of tumor cells to escape immunosurveillance checkpoints. EXPERIMENTAL DESIGN: Over 150 primary non-small cell lung cancers, including pulmonary sarcomatoid carcinomas, were tested for the levels of HLA-I complex, PD-L1, tumor-infiltrating CD8+ lymphocytes and alterations in main LC genes...
June 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Léa Paolini, Caroline Poli, Simon Blanchard, Thierry Urban, Anne Croué, Marie-Christine Rousselet, Sarah Le Roux, Nathalie Labarrière, Pascale Jeannin, José Hureaux
BACKGROUND: Immune checkpoint inhibitors (ICI) target T cell inhibitory pathways that are responsible for cancer tolerance by down-modulating immune functions. ICI have revolutionized patients care with lung cancer. Nevertheless, restoring endogenous antitumor T-cell responses can induce immune related adverse events, such as sarcoidosis. CASE PRESENTATION: We report here the first case of a thoracic and cutaneous sarcoid-like reaction in a patient with a relapsing unresectable non-small cell lung cancer (NSCLC) treated with nivolumab, an anti-PD-1 mAb...
June 13, 2018: Journal for Immunotherapy of Cancer
Daisuke Watanabe, Fumi Goshima
Oncolytic virotherapy is a kind of antitumor therapy using viruses with natural or engineered tumor-selective replication to intentionally infect and kill tumor cells. An early clinical trial has been performed in the 1950s using wild-type and non-engineered in vitro-passaged virus strains and vaccine strains (first generation oncolytic viruses). Because of the advances in biotechnology and virology, the field of virotherapy has rapidly evolved over the past two decades and innovative recombinant selectivity-enhanced viruses (second generation oncolytic viruses)...
2018: Advances in Experimental Medicine and Biology
Sabrina A Hogan, Mitchell P Levesque, Phil F Cheng
The recent emergence of cancer immunotherapies initiated a significant shift in the clinical management of metastatic melanoma. Prior to 2011, melanoma patients only had palliative treatment solutions which offered little to no survival benefit. In 2018, with immunotherapy, melanoma patients can now contemplate durable or even complete remission. Treatment with novel immune checkpoint inhibitors, anti-cytotoxic T-lymphocyte protein 4 and anti-programmed cell death protein 1, clearly result in superior median and long-term survivals compared to standard chemotherapy; however, more than half of the patients do not respond to immune checkpoint blockade...
2018: Frontiers in Oncology
Chigusa Morizane, Makoto Ueno, Masafumi Ikeda, Takuji Okusaka, Hiroshi Ishii, Junji Furuse
Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gall bladder, ampullary carcinoma and intrahepatic cholangiocarcinoma are often identified at an advanced stage and have poor prognoses. Although effective chemotherapy regimens are needed, their development remains unsatisfactory. From the results of a phase III clinical trial (ABC-02 trial), gemcitabine plus cisplatin is the standard first-line chemotherapeutic regimen for advanced biliary tract cancer. A phase III trial of gemcitabine plus cisplatin vs...
June 11, 2018: Japanese Journal of Clinical Oncology
Koji Kono, Kousaku Mimura, Reo Yamada, Daisuke Ujiie, Suguru Hayase, Takeshi Tada, Hiroyuki Hanayama, Aung Kyi Thar Min, Masahiko Shibata, Tomoyuki Momma, Zenichirou Saze, Shinji Ohki
BACKGROUND: Immunotherapy has become a promising treatment strategy for cancer. Immune checkpoint blockade with anti-CTLA4 mAb and anti-PD-1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple cancer types including esophageal squamous cell carcinoma (ESCC). There are several clinical trials using anti-PD1 mAb for ESCC in early phases and the results are currently promising...
January 2018: Esophagus: Official Journal of the Japan Esophageal Society
Dharmesh Gopalakrishnan, Vadim S Koshkin, Moshe C Ornstein, Athanasios Papatsoris, Petros Grivas
Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor. Since the peak incidence of bladder cancer is in the eighth decade of life and beyond, medical comorbidities may often limit the use of chemotherapy. Immune checkpoint inhibitors with their favorable toxicity profiles and notable antitumor activity have ushered in a new era in the treatment of advanced urothelial cancer (UC) with five agents targeting the PD-1/PD-L1 pathway being recently approved by the US Food and Drug administration...
2018: Therapeutics and Clinical Risk Management
Kelly G Paulson, Shailender Bhatia
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer. The clinical impact of MCC has been increasing due to steadily rising incidence rates. Since 2001, more than 24,000 cases of MCC have been reported to the US National Program of Cancer Registries database, and in 2018, more than 2,500 incident cases are expected. MCC is highly aggressive, and one-third of patients will either present with or develop metastatic disease. Outcomes in patients with metastatic MCC have historically been poor; median time to progression with cytotoxic chemotherapy is only 3 months...
June 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Satoshi Nakagawa, Satoshi Serada, Reisa Kakubari, Kosuke Hiramatsu, Takahito Sugase, Shinya Matsuzaki, Satoko Matsuzaki, Yutaka Ueda, Kiyoshi Yoshino, Tomoharu Ohkawara, Minoru Fujimoto, Tadamitsu Kishimoto, Tadashi Kimura, Tetsuji Naka
Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths and novel therapeutic strategies are required. Programmed cell death 1 and programmed cell death ligand 1 (PD-L1), which are key mediators of host immune tolerance, are associated with OvCa progression. Recent evidence indicates the importance of IFN-γ-induced PD-L1 for immune tolerance in OvCa. This study aimed to reveal the therapeutic potential of suppressor of cytokine signaling 1 (SOCS-1), an endogenous inhibitor of the janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, for the treatment of OvCa...
June 11, 2018: Molecular Cancer Therapeutics
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