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immune-checkpoint blockers

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https://www.readbyqxmd.com/read/28551360/immunotherapeutic-properties-of-chemotherapy
#1
REVIEW
Carole Fournier, Thaiz Rivera Vargas, Tiffany Martin, Andréa Melis, Lionel Apetoh
Impressive remissions driven by immunological checkpoint blockade in cancer patients have prompted the scientific community to investigate afresh the crosstalk between cancer cells and the patient's immune system. Preclinical and clinical studies have highlighted that the anticancer efficacy of some conventional chemotherapeutics is based on their ability to restore anticancer immune responses. The current challenge is to understand and circumvent immune resistance mechanisms to chemo- and immunotherapies to design relevant immunotherapy and chemotherapy combinations...
May 24, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#2
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521532/new-antivirals-for-the-treatment-of-chronic-hepatitis-b
#3
Vincent Soriano, Pablo Barreiro, Laura Benitez, Jose M Peña, Carmen de Mendoza
Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription...
May 18, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28499411/paraneoplastic-acral-vascular-syndrome-in-a-patient-with-metastatic-melanoma-under-immune-checkpoint-blockade
#4
Thilo Gambichler, Stefanie Strutzmann, Andrea Tannapfel, Laura Susok
BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested. CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla...
May 12, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28459943/circulating-tumor-dna-changes-for-early-monitoring-of-anti-pd1-immunotherapy-a-proof-of-concept-study
#5
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/28361267/anti-angiogenesis-for-cancer-revisited-is-there-a-role-for-combinations-with-immunotherapy
#6
REVIEW
Rakesh R Ramjiawan, Arjan W Griffioen, Dan G Duda
Angiogenesis is defined as the formation of new blood vessels from preexisting vessels and has been characterized as an essential process for tumor cell proliferation and viability. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve tumor of nutrients and oxygen, primarily through blockade of VEGF/VEGFR signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, alone or in combination with chemotherapy or other targeted therapies...
May 2017: Angiogenesis
https://www.readbyqxmd.com/read/28346400/t-lymphocyte-homing-an-underappreciated-yet-critical-hurdle-for-successful-cancer-immunotherapy
#7
Robert Sackstein, Tobias Schatton, Steven R Barthel
Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue...
June 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28315206/otorhinolaryngological-toxicities-of-new-drugs-in-oncology
#8
REVIEW
Dana M Hartl, Daphné Morel, Erika Saavedra, Christophe Massard, Alessandra Rinaldo, Nabil F Saba, Alfio Ferlito, Jean-Charles Soria
Many new or relatively new cancer drugs-personalized anticancer agents-have been approved for use in various clinical settings in oncology or are still under evaluation in clinical trials. Targeted therapies as well as new immune checkpoint blockers have toxicity profiles that differ from conventional cytotoxic chemotherapy, and many can cause adverse effects that affect the mouth and pharynx, the nasal cavities, and the larynx. This review aims to provide an overview of current knowledge concerning these side effects and contemporary management...
March 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28300768/tim-3-as-a-target-for-cancer-immunotherapy-and-mechanisms-of-action
#9
REVIEW
Wenwen Du, Min Yang, Abbey Turner, Chunling Xu, Robert L Ferris, Jianan Huang, Lawrence P Kane, Binfeng Lu
Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy...
March 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28283197/making-targeted-therapy-compatible-with-checkpoint-immunotherapy
#10
Ariel Fernández
Immune checkpoint blockades induced by antibodies are revolutionizing cancer therapy. Combinations of checkpoint immunotherapies with kinase inhibitors (KIs) are being clinically evaluated as oncogenic mutations arise. Off-target KI cross-reactivity will often compromise synergistic efficacy, with KIs suppressing T-cell functionalities that checkpoint blockers are purportedly boosting. This incompatibility may be removed through molecular optimization.
March 8, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28280600/structural-basis-of-a-novel-pd-l1-nanobody-for-immune-checkpoint-blockade
#11
Fei Zhang, Hudie Wei, Xiaoxiao Wang, Yu Bai, Pilin Wang, Jiawei Wu, Xiaoyong Jiang, Yugang Wang, Haiyan Cai, Ting Xu, Aiwu Zhou
The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28256019/ipilimumab-has-efficacy-in-metastatic-merkel-cell-carcinoma-a-case-series-of-five-patients
#12
J K Winkler, A Dimitrakopoulou-Strauss, C Sachpekidis, A Enk, J C Hassel
Immunotherapy with immune checkpoint blockers such as the CTLA-4 antibody ipilimumab and PD-1 antibodies has revolutionized oncological treatment options(1) . MCC is an immunogenic tumor and the efficacy of PD-1 blockade has recently been demonstrated(2,3,4) . Here, we present a retrospective analysis of five patients with metastatic MCC individually treated with ipilimumab between 2012 and 2015. Administration of four cycles (3 mg/kg every three weeks) was planned. Informed consent was obtained from all patients...
March 3, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28254528/candidate-immune-biomarkers-for-radioimmunotherapy
#13
REVIEW
Antonin Levy, Giulia Nigro, Philippe J Sansonetti, Eric Deutsch
Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28229253/the-biology-of-uveal-melanoma
#14
Adriana Amaro, Rosaria Gangemi, Francesca Piaggio, Giovanna Angelini, Gaia Barisione, Silvano Ferrini, Ulrich Pfeffer
Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11...
March 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28197360/enhancing-the-clinical-coverage-and-anticancer-efficacy-of-immune-checkpoint-blockade-through-manipulation-of-the-gut-microbiota
#15
Jonathan M Pitt, Marie Vétizou, Ivo Gomperts Boneca, Patricia Lepage, Mathias Chamaillard, Laurence Zitvogel
Although anticancer therapy with immune checkpoint blockers has seen unprecedented success, it fails to control neoplasia in most patients and often causes immune-related adverse events (irAEs). Our recent research shows the immunostimulatory and antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species of the gut microbiota, signifying novel approaches to improve such immunotherapies.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/27911273/robust-detection-of-immune-transcripts-in-ffpe-samples-using-targeted-rna-sequencing
#16
Benjamin E Paluch, Sean T Glenn, Jeffrey M Conroy, Antonios Papanicolau-Sengos, Wiam Bshara, Angela R Omilian, Elizabeth Brese, Mary Nesline, Blake Burgher, Jonathan Andreas, Kunle Odunsi, Kevin Eng, Ji He, Maochun Qin, Mark Gardner, Lorenzo Galluzzi, Carl D Morrison
Current criteria for identifying cancer patients suitable for immunotherapy with immune checkpoint blockers (ICBs) are subjective and prone to misinterpretation, as they mainly rely on the visual assessment of CD274 (best known as PD-L1) expression levels by immunohistochemistry (IHC). To address this issue, we developed a RNA sequencing (RNAseq)-based approach that specifically measures the abundance of immune transcripts in formalin-fixed paraffin embedded (FFPE) specimens. Besides exhibiting superior sensitivity as compared to whole transcriptome RNAseq, our assay requires little starting material, implying that it is compatible with RNA degradation normally caused by formalin...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27795504/dendritic-cell-and-cancer-immune-checkpoint
#17
REVIEW
Terufumi Kubo, Yoshihiko Hirohashi, Toshihiko Torigoe
  Extensive research over 100 years has clarified that cancers are surely suppressed by human immune system. Unfortunately, a number of clinical trials with various approaches have fallen short of clinical application because of the lack of significant anti-tumor effect. However, recent approved immune checkpoint inhibitors, namely PD-1 and CTLA-4 blockers, provide even better prognosis than existing chemotherapy in patients with certain types of cancer. There is no doubt that immunotherapy is becoming a standard treatment as well as surgery, chemotherapy and radiotherapy...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27786364/usefulness-of-serum-5-s-cysteinyl-dopa-as-a-biomarker-for-predicting-prognosis-and-detecting-relapse-in-patients-with-advanced-stage-malignant-melanoma
#18
Hiroshi Umemura, Osamu Yamasaki, Tatsuya Kaji, Masaki Otsuka, Kenji Asagoe, Minoru Takata, Keiji Iwatsuki
With the recent development of novel molecular targeted drugs for advanced stage malignant melanoma (MM), including RAF and mitogen-activated protein kinase kinase inhibitors and immune checkpoint blockers, the early detection of relapse is important for managing patients with MM. In this study, we retrospectively analyzed two conventional serum biomarkers, 5-S-cysteinyl-dopa and lactate dehydrogenase, in patients with MM (n = 140) who were treated at a single Japanese institute from June 2007 to June 2015...
October 27, 2016: Journal of Dermatology
https://www.readbyqxmd.com/read/27764686/concurrent-irradiation-with-the-anti-programmed-cell-death-ligand-1-immune-checkpoint-blocker-durvalumab-single-centre-subset-analysis-from-a-phase-1-2-trial
#19
Antonin Levy, Christophe Massard, Jean-Charles Soria, Eric Deutsch
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR])...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27757313/trial-watch-immunotherapy-plus-radiation-therapy-for-oncological-indications
#20
REVIEW
Erika Vacchelli, Norma Bloy, Fernando Aranda, Aitziber Buqué, Isabelle Cremer, Sandra Demaria, Alexander Eggermont, Silvia Chiara Formenti, Wolf Hervé Fridman, Jitka Fucikova, Jérôme Galon, Radek Spisek, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects...
2016: Oncoimmunology
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