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Immuno checkpoint

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https://www.readbyqxmd.com/read/29029813/innovative-therapy-monoclonal-antibodies-and-beyond
#1
M Di Nicola, L Apetoh, M Bellone, M P Colombo, G Dotti, S Ferrone, M Muscolini, J Hiscott, A Anichini, S M Pupa, F de Braud, M Del Vecchio
The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond" Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the meeting were focused on: 1) Preclinical assays and novel biotargets; and 2) monoclonal antibodies, cell therapies and targeted molecules. Between these two sessions, a lecture entitled "HLA-antigens modulation and response to immune checkpoint inhibitor immunotherapy" was also presented. Despite the impressive successes in cancer immunotherapy in recent years, the response to immune based interventions occurs only in a minority of patients (∼20%)...
October 5, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29020960/perspectives-in-immunotherapy-meeting-report-from-the-immunotherapy-bridge-napoli-november-30th-2016
#2
Paolo A Ascierto, Bruno Daniele, Hans Hammers, Vera Hirsh, Joseph Kim, Lisa Licitra, Rita Nanda, Sandro Pignata
The complex interactions between the immune system and tumors lead the identification of key molecules that govern these interactions: immunotherapeutics were designed to overcome the mechanisms broken by tumors to evade immune destruction. After the substantial advances in melanoma, immunotherapy currently includes many other type of cancers, but the melanoma lesson is essential to progress in other type of cancers, since immunotherapy is potentially improving clinical outcome in various solid and haematologic malignancies...
October 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28982322/pd-1-pd-l1-inhibitors-for-immuno-oncology-from-antibodies-to-small-molecules
#3
Qiaohong Geng, Peifu Jiao, Peng Jin, Gaoxing Su, Jinlong Dong, Bing Yan
BACKGROUND: The recent regulatory approvals of immune checkpoint protein inhibitors such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types...
October 4, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28971564/small-molecules-drive-big-improvements-in-immuno-oncology-therapies
#4
Klaus Urbahns, Bayard R Huck, Lisa Kötzner
Immuno-oncology therapies have the potential to revolutionize the armamentarium of available cancer treatment regimens. In order to further improve clinical response rates, researchers are looking for novel combination treatments, using checkpoint blockade as a backbone of the treatment. This review highlights the significance of small molecules in this approach, which holds promise to provide increased benefit to cancer patients.
October 3, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28961038/focused-ultrasound-for-immuno-adjuvant-treatment-of-pancreatic-cancer-an-emerging-clinical-paradigm-in-the-era-of-personalized-oncotherapy
#5
Ezekiel Maloney, Tanya Khokhlova, Venu G Pillarisetty, George R Schade, Elizabeth A Repasky, Yak-Nam Wang, Lorenzo Giuliani, Matteo Spring, Joo Ha Hwang
Current clinical treatment regimens, including many emergent immune strategies (e.g., checkpoint inhibitors) have done little to affect the devastating course of pancreatic ductal adenocarcinoma (PDA). Clinical trials for PDA often employ multi-modal treatment, and have started to incorporate stromal-targeted therapies, which have shown promising results in early reports. Focused ultrasound (FUS) is one such therapy that is uniquely equipped to address local and systemic limitations of conventional cancer therapies as well as emergent immune therapies for PDA...
September 29, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28938090/small-molecule-targets-in-immuno-oncology
#6
REVIEW
Dashyant Dhanak, James P Edwards, Ancho Nguyen, Peter J Tummino
Advances in understanding the role and molecular mechanisms underlying immune surveillance and control of (pre)malignancies is revolutionizing clinical practice in the treatment of cancer. Presently, multiple biologic drugs targeting the immune checkpoint proteins PD(L)1 or CTLA4 have been approved and/or are in advanced stages of clinical development for many cancers. In addition, combination therapy with these agents and other immunomodulators is being intensively explored with the aim of improving primary response rates or prolonging overall survival...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28935020/-novel-immuno-oncology-therapy-current-status-of-clinical-research-and-prospect-of-application
#7
Shijia Zhang, Shengxiang Ren
Recently, immune-oncologic therapy advanced rapidly and has been defined as another option, following surgery, radiotherapy, chemotherapy and molecular targeted therapy, for treatment of malignant diseases. To date, several immune checkpoint inhibitors and compounds have been approved to treat various of malignant diseases with efficiency. Meanwhile, more and more potential therapeutic targets in processes of the cancer immunity have been noticed. We aimed to summarize the research status and clinical prospects of novel immune-oncologic treatment agencies targeted to different steps of the cancer-immunity cycle...
September 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28931635/a-computational-multiscale-agent-based-model-for-simulating-spatio-temporal-tumour-immune-response-to-pd1-and-pdl1-inhibition
#8
Chang Gong, Oleg Milberg, Bing Wang, Paolo Vicini, Rajesh Narwal, Lorin Roskos, Aleksander S Popel
When the immune system responds to tumour development, patterns of immune infiltrates emerge, highlighted by the expression of immune checkpoint-related molecules such as PDL1 on the surface of cancer cells. Such spatial heterogeneity carries information on intrinsic characteristics of the tumour lesion for individual patients, and thus is a potential source for biomarkers for anti-tumour therapeutics. We developed a systems biology multiscale agent-based model to capture the interactions between immune cells and cancer cells, and analysed the emergent global behaviour during tumour development and immunotherapy...
September 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#9
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28912090/immuno-oncology-and-its-opportunities-for-interventional-radiologists-immune-checkpoint-inhibition-and-potential-synergies-with-interventional-oncology%C3%A2-procedures
#10
REVIEW
Ryan M Hickey, Laura M Kulik, Halla Nimeiri, Aparna Kalyan, Sheetal Kircher, Kush Desai, Ahsun Riaz, Robert J Lewandowski, Riad Salem
Immunotherapy, specifically the use of immune checkpoint inhibitors, offers a new approach to fighting cancer. Although the results of treatment with immune checkpoint inhibition alone have been remarkable for certain cancers, these results are not universal. Preclinical and early clinical studies indicate the potential for synergistic effects when immune checkpoint inhibition is combined with immunogenic local therapies such as ablation and embolization. This review offers an overview of immunology as it relates to immune checkpoint inhibition and the possibilities for synergy when combined with interventional radiology treatments...
September 12, 2017: Journal of Vascular and Interventional Radiology: JVIR
https://www.readbyqxmd.com/read/28864727/immuno-oncology-clinical-trial-design-limitations-challenges-and-opportunities
#11
EDITORIAL
Christina S Baik, Eric H Rubin, Patrick M Forde, Janice M Mehnert, Deborah Collyar, Marcus O Butler, Erica L Dixon, Laura Q M Chow
Recent advances in immuno-oncology and regulatory approvals have been rapid and paradigm shifting in many difficult-to-treat malignancies. Despite immune checkpoint inhibitor therapy becoming the standard of care across multiple tumor types, there are many unanswered questions that need to be addressed before this therapeutic modality can be fully harnessed. Areas of limitations include treatment of patients not sufficiently represented in clinical trials, uncertainty of the optimal treatment dosing and duration, and lack of understanding regarding long-term immune related toxicities and atypical tumor responses...
September 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28864726/from-famine-to-feast-developing-early-phase-combination-immunotherapy-trials-wisely
#12
EDITORIAL
Daphne Day, Arta M Monjazeb, Elad Sharon, S Percy Ivy, Eric H Rubin, Gary L Rosner, Marcus O Butler
Not until the turn of this century has immunotherapy become a fundamental component of cancer treatment. While monotherapy with immune modulators, such as immune checkpoint inhibitors, provides a subset of patients with durable clinical benefit and possible cure, combination therapy offers the potential for antitumor activity in a greater number of patients. The field of immunology has provided us with a plethora of potential molecules and pathways to target. This abundance makes it impractical to empirically test all possible combinations efficiently...
September 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28837184/checkpoint-inhibitors-a-cutting-edge-in-oncology
#13
REVIEW
C Jago
The checkpoint inhibitor field, and indeed the whole of immuno-oncology, is fast-paced and fascinating, with huge clinical and commercial potential. The challenge in the coming years will be to define the best type and combination of immunotherapy, and the best target population to receive it. Keytruda's ground-breaking approval for a biomarker-based rather than location-based indication is a solid step in this direction, and is likely to be followed by other such approvals. As the field develops, it is to be hoped that immuno-oncology therapeutics will continue to deliver the significant improvements in patient outcome that have been seen so far...
July 2017: Drugs of Today
https://www.readbyqxmd.com/read/28835379/sequential-multiple-assignment-randomized-trial-designs-in-immuno-oncology-research
#14
Kelley M Kidwell, Michael A Postow, Katherine S Panageas
Clinical trials investigating immune checkpoint inhibitors have led to the approval of anti-CTLA-4 (cytotoxic T-lymphocyte antigen-4), anti-PD-1 (programmed death-1) and anti-PD-L1 (PD-ligand 1) drugs by the United States Food & Drug Administration (FDA) for numerous tumor types. In the treatment of metastatic melanoma, combinations of checkpoint inhibitors are more effective than single agent inhibitors, but combination immunotherapy is associated with increased frequency and severity of toxicity. There are questions about the use of combination immunotherapy or single agent anti-PD-1 as initial therapy and the number of doses of either approach required to sustain a response...
August 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28825923/immunotherapy-for-metastatic-prostate-cancer-immuno-cold-or-the-tip-of-the-iceberg
#15
Andrew L Laccetti, Sumit K Subudhi
PURPOSE OF REVIEW: Metastatic castration-resistant prostate cancer is in critical need of new and innovative treatment strategies. Since the approval of sipuleucel-T, the investigatory climate of prostate cancer immunotherapy has been rapidly evolving with promising developments in vaccine and immune checkpoint therapies. RECENT FINDINGS: Sipuleucel-T remains the first and only therapeutic cancer vaccine approved for its survival benefit in metastatic castration-resistant prostate cancer...
August 18, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28822058/immune-dysfunction-in-non-hodgkin-lymphoma-avenues-for-new-immunotherapy-based-strategies
#16
REVIEW
Lorenzo Falchi
PURPOSE OF THIS REVIEW: The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies. RECENT FINDINGS: In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors...
August 18, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#17
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819209/synergistic-immuno-photothermal-nanotherapy-symphony-for-the-treatment-of-unresectable-and-metastatic-cancers
#18
Yang Liu, Paolo Maccarini, Gregory M Palmer, Wiguins Etienne, Yulin Zhao, Chen-Ting Lee, Xiumei Ma, Brant A Inman, Tuan Vo-Dinh
Metastatic spread is the mechanism in more than 90 percent of cancer deaths and current therapeutic options, such as systemic chemotherapy, are often ineffective. Here we provide a proof of principle for a novel two-pronged modality referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) having the potential to safely eradicate both primary tumors and distant metastatic foci. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)-mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815043/the-mek-inhibitor-selumetinib-complements-ctla-4-blockade-by-reprogramming-the-tumor-immune-microenvironment
#19
Edmund Poon, Stefanie Mullins, Amanda Watkins, Geoffrey S Williams, Jens-Oliver Koopmann, Gianfranco Di Genova, Marie Cumberbatch, Margaret Veldman-Jones, Shaun E Grosskurth, Vasu Sah, Alwin Schuller, Corrine Reimer, Simon J Dovedi, Paul D Smith, Ross Stewart, Robert W Wilkinson
BACKGROUND: T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28812378/bevacizumab-in-advanced-lung-cancer-state-of-the-art
#20
Sandra Assoun, Solenn Brosseau, Christelle Steinmetz, Valérie Gounant, Gérard Zalcman
Despite recent advances in metastatic lung cancer treatment with the advent of immune checkpoint inhibitors and molecules targeting addictive genomic abnormalities, prognosis of most of the patients remains unfavorable. Combination approaches with older drugs, such as bevacizumab, should be thus envisioned. Bevacizumab is a monoclonal anti-VEGF antibody, approved by the US FDA and the EMA in first-line and maintenance settings of advanced nonsquamous non-small-cell lung cancer (NSCLC) treatment, in association with platinum-based chemotherapy...
August 16, 2017: Future Oncology
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