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A K S Salama, S J Moschos
BACKGROUND: Cancers escape immune surveillance via distinct mechanisms that involve central (negative selection within the thymus) or peripheral (lack of costimulation, receipt of death/anergic signals by tumor, immunoregulatory cell populations) immune tolerance. During the 1990s, moderate clinical benefit was seen using several cytokine therapies for a limited number of cancers. Over the past 20 years, extensive research has been performed to understand the role of various components of peripheral immune tolerance, with the co-inhibitory immune checkpoint molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand (PD-L1) being the most well characterized at preclinical and clinical levels...
October 13, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Peter Ellmark, Sara M Mangsbo, Christina Furebring, Per Norlén, Thomas H Tötterman
The most important goals for the field of immuno-oncology are to improve the response rate and increase the number of tumor indications that respond to immunotherapy, without increasing adverse side effects. One approach to achieve these goals is to use tumor-directed immunotherapy, i.e., to focus the immune activation to the most relevant part of the immune system. This may improve anti-tumor efficacy as well as reduce immune-related adverse events. Tumor-directed immune activation can be achieved by local injections of immune modulators in the tumor area or by directing the immune modulator to the tumor using bispecific antibodies...
October 6, 2016: Cancer Immunology, Immunotherapy: CII
P Fang, X Rao, J Wang, D Maru, S H Lin
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Francesco Schettini, Mario Giuliano, Sabino De Placido, Grazia Arpino
Triple-negative breast cancer (TNBC) accounts for ∼10-20% of breast cancers and is associated with relatively poor prognosis, earlier disease recurrence and higher number of visceral metastases. Despite an increasing understanding of the molecular heterogeneity of TNBC, clinical trials of targeted agents have thus far been disappointing; chemotherapy, in particular with anthracycline and taxanes, remains the backbone medical management for both early and metastatic TNBC. Nab-paclitaxel is a solvent-free, albumin-bound, nanoparticle formulation of paclitaxel and represents a novel formulation of an established, effective chemotherapeutic agent...
September 12, 2016: Cancer Treatment Reviews
Catherine A Evans, Tao Liu, André Lescarbeau, Somarajan J Nair, Louis Grenier, Johan A Pradeilles, Quentin Glenadel, Thomas Tibbitts, Ann M Rowley, Jonathan P DiNitto, Erin E Brophy, Erin L O'Hearn, Janid A Ali, David G Winkler, Stanley I Goldstein, Patrick O'Hearn, Christian M Martin, Jennifer G Hoyt, John R Soglia, Culver Cheung, Melissa M Pink, Jennifer L Proctor, Vito J Palombella, Martin R Tremblay, Alfredo C Castro
Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors.
September 8, 2016: ACS Medicinal Chemistry Letters
Nafees N Malik, Matthew B Durdy
No abstract text is available yet for this article.
October 2016: Drug Discovery Today
Stephen J Blake, William C Dougall, John J Miles, Michele W L Teng, Mark J Smyth
The receptors CD96 and TIGIT are expressed on the surface of T and natural killer (NK) cells, and recent studies suggest both play important inhibitory roles in immune function. CD96 has been shown to modulate immune cell activity in mice, with Cd96(-)(/)(-) mice displaying hypersensitive NK-cell responses to immune challenge and significant tumor resistance. TIGIT overexpression has been shown to reduce NK-cell-mediated cytotoxicity. TIGIT is also upregulated on T cells during cancer and chronic viral infection, with expression associated with effector T-cell exhaustion and increased regulatory T-cell suppression...
September 12, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rachel Thomas
Patients diagnosed with advanced non-small-cell lung cancer (NSCLC) (either squamous or non-squamous) have previously had limited treatment options after progression on chemotherapy. With the emergence of new drugs, particularly in the immuno-oncology setting, this is now changing. Recent clinical trial evidence demonstrates that compared with docetaxel, patients who received nivolumab had better overall survival and also significantly fewer grade 3-4 adverse events. This article reviews the clinical trial data for nivolumab and provides an overview of how this drug works...
September 8, 2016: British Journal of Nursing: BJN
Leila Khoja, Bishal Gyawali
Immuno-oncology has changed the landscape of cancer treatment in recent years. Immune checkpoint inhibitors (ICI) have shown survival advantage with long term remissions in a variety of cancers. However, there is another approach to harnessing the power of the immune system in combating cancer: the adoptive cell therapy (ACT) strategy. Although ACT is restricted to small specialized centres and has yet to deliver as much success as ICI, some important results were presented at this year's ASCO meeting. Important lessons have been learned from these studies, including the prospects and challenges ahead...
2016: Ecancermedicalscience
Filippo Lococo, Gianluigi Bajocchi, Andrea Caruso, Riccardo Valli, Tommaso Ricchetti, Giorgio Sgarbi, Carlo Salvarani
BACKGROUND: Thymoma is a T cell neoplasm arising from the thymic epithelium that due to its immunological role, frequently undercover derangements of immunity such a tumors and autoimmune diseases. METHODS: Herein, we report, to the best of our knowledge, the first description of an association between thymoma and adult onset Still disease (AOSD) in a 47-year-old man. The first one was occasionally detected 4 years later the diagnosis of AOSD, and surgically removed via right lateral thoracotomy...
September 2016: Medicine (Baltimore)
James W Larrick, Mark R Alfenito, Jamie K Scott, Paul W H I Parren, Dennis R Burton, Andrew R M Bradbury, Cynthia A Lemere, Anne Messer, James S Huston, Paul J Carter, Trudi Veldman, Kerry A Chester, Janine Schuurman, Gregory P Adams, Janice M Reichert
Antibody Engineering & Therapeutics, the largest meeting devoted to antibody science and technology and the annual meeting of The Antibody Society, will be held in San Diego, CA on December 11-15, 2016. Each of 14 sessions will include six presentations by leading industry and academic experts. In this meeting preview, the session chairs discuss the relevance of their topics to current and future antibody therapeutics development. Session topics include bispecifics and designer polyclonal antibodies; antibodies for neurodegenerative diseases; the interface between passive and active immunotherapy; antibodies for non-cancer indications; novel antibody display, selection and screening technologies; novel checkpoint modulators / immuno-oncology; engineering antibodies for T-cell therapy; novel engineering strategies to enhance antibody functions; and the biological Impact of Fc receptor engagement...
August 24, 2016: MAbs
Nicholas G Kounis, Ioanna Koniari, George Hahalis
No abstract text is available yet for this article.
November 15, 2016: International Journal of Cardiology
B Kiernan
Immuno-oncology (I/O) is changing the way that we approach cancer therapy. As precision medicine comes to the forefront, clinical researchers are beginning to home in on tumors with targeted therapies, focusing on those that have been previously resistant to treatment. This has been accom¬plished with chemical agents in small cancer subsets; how¬ever, immunotherapy seeks to harness the mechanisms of our own immune system to target cancer and its pathways.
July 2016: Drugs of Today
Leo Li-Ying Chan, Tim Smith, Kendra A Kumph, Dmitry Kuksin, Sarah Kessel, Olivier Déry, Scott Cribbes, Ning Lai, Jean Qiu
To ensure cell-based assays are performed properly, both cell concentration and viability have to be determined so that the data can be normalized to generate meaningful and comparable results. Cell-based assays performed in immuno-oncology, toxicology, or bioprocessing research often require measuring of multiple samples and conditions, thus the current automated cell counter that uses single disposable counting slides is not practical for high-throughput screening assays. In the recent years, a plate-based image cytometry system has been developed for high-throughput biomolecular screening assays...
October 2016: Cytotechnology
Samuel J Harris, Jessica Brown, Juanita Lopez, Timothy A Yap
There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer, immune checkpoint inhibitors also appear to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance...
June 2016: Cancer Biology & Medicine
Jennifer J Peterson, Susan K Steele-Moses
BACKGROUND: Immunotherapy has had a long history in cancer treatment and, with recent breakthroughs, new drugs are available that have shown promising results. OBJECTIVES: The current article discusses an overview of immune function, including immunoediting and the theory of immune checkpoints, as well as specific drugs that have been approved as immune checkpoint inhibitors. Additional discussion includes a review of nursing implications and administration, side effects, adverse events, and the future of immuno-oncology...
August 1, 2016: Clinical Journal of Oncology Nursing
Thorsten Fuereder
Over the past years immuno-oncology has evolved and become a novel promising strategy for cancer therapy. Immune checkpoint inhibitors such as pembrolizumab or nivolumab, which target the interaction between programmed death receptor 1/programmed death ligand 1 (PD-1/PDL-1) and PDL-2, have been recently approved for the treatment of various malignancies and are currently being investigated in clinical phase III trials for head and neck squamous cell carcinoma (HNSCC). Data available from these trials indicate substantial activity accompanied by a favorable safety and toxicity profile in this patient population...
2016: Memo
Theresa M Medina, Karl D Lewis
Metastatic melanoma is an aggressive, rapidly progressive disease which historically had very few effective treatment options. However, since 2011, the therapeutic landscape of melanoma has undergone a dramatic transformation with two distinct approaches and has catalyzed the successful advancement in the clinical field of immuno-oncology. In addition, the recognition of a key oncogenic driver mutation in melanoma, BRAF, stimulated the development of multiple potent kinase inhibitors which has also influenced the expansion and use of targeted agents in the practice of oncology...
2016: OncoTargets and Therapy
Sophia M Wilden, Berenice M Lang, Peter Mohr, Stephan Grabbe
It has been known for decades that the immune system is able to detect and destroy tumor cells. In the past, this knowledge - mostly acquired through animal experiments - could not be used to benefit our patients, because immuno-oncological therapeutic approaches in humans had constantly failed over recent decades. With the exception of adjuvant interferon therapy, none of these approaches had found its way into everyday clinical practice, and only very few patients were able to enjoy long-term survival associated with good quality of life...
July 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Aaron M Newman, Ash A Alizadeh
Tumors are complex ecosystems comprised of diverse cell types including malignant cells, mesenchymal cells, and tumor-infiltrating leukocytes (TILs). While TILs are well known to play important roles in many aspects of cancer biology, recent developments in immuno-oncology have spurred considerable interest in TILs, particularly in relation to their optimal engagement by emerging immunotherapies. Traditionally, the enumeration of TIL phenotypic diversity and composition in solid tumors has relied on resolving single cells by flow cytometry and immunohistochemical methods...
August 2016: Current Opinion in Immunology
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