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Immunology oncological

Wen-Ting K Tsai, Anna M Wu
The exquisite specificity of antibodies and antibody fragments renders them excellent agents for targeted delivery of radionuclides. Radiolabeled antibodies and fragments have been successfully used for molecular imaging and radioimmunotherapy (RIT) of cell-surface targets in oncology and immunology. Protein engineering has been employed for antibody humanization essential for clinical applications, as well as optimization of important characteristics including pharmacokinetics, biodistribution, and clearance...
March 14, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
Yesi Shi, Xin Pang, Junqing Wang, Gang Liu
TRAIL is a member of the tumor necrosis factor superfamily that can largely trigger apoptosis in a wide variety of cancer cells, but not in normal cells. However, insufficient exposure to cancer tissues or cells and drug resistance has severely impeded the clinical application of TRAIL. Recently, nanobiotechnology has brought about a revolution in advanced drug delivery for enhanced anticancer therapy using TRAIL. With the help of materials science, immunology, genetic engineering, and protein engineering, substantial progress is made by expressing fusion proteins with TRAIL, engineering TRAIL on biological membranes, and loading TRAIL into functional nanocarriers or conjugating it onto their surfaces...
March 12, 2018: Advanced Healthcare Materials
Peter Hart, Alastair Copland, Gil Reynolds Diogo, Shane Harris, Ralf Spallek, Wulf Oehlmann, Mahavir Singh, Juan Basile, Martin Rottenberg, Matthew John Paul, Rajko Reljic
Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Calmette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Aglaia Domouchtsidou, Vahé Barsegian, Stefan P Mueller, Jan Best, Judith Ertle, Sotiria Bedreli, Peter A Horn, Andreas Bockisch, Monika Lindemann
The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
P J Schuler, C Brunner, T K Hoffmann
As immunotherapy is becoming increasingly important in the treatment of head and neck cancer, a fundamental understanding of the immunological relationships in the tumor microenvironment is required. The importance of tumor-infiltrating B cells (TIL-B) has been largely neglected so far. In the current literature, however, a significant influence of B cells on tumor growth is described, so that this cell population is now also perceived as a therapeutic target structure. Regulatory B cells (Breg ) represent a subset of B cells with immunosuppressive properties...
March 2, 2018: HNO
N Cirillo
The discovery of an oral glucocorticoid system has provided novel conceptual frameworks for understanding the effects of endogenous and exogenous corticosteroids in the oral cavity. For example, liquorice derivatives have long been used in the treatment of oral inflammatory conditions and it is now known that a chief constituent of liquorice root, glycyrrhetinic acid, inhibits 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2 thus increasing local cortisol levels. Hence, targeting the local interconversion between inactive cortisone and active cortisol by 11β-HSD inhibitors/activators offers potentially advantageous strategies for the treatment of oral inflammatory and autoimmune conditions...
March 2018: Oral Diseases
Inmaculada Hernandez, Samuel W Bott, Anish S Patel, Collin G Wolf, Alexa R Hospodar, Shivani Sampathkumar, William H Shrank
OBJECTIVES: The rising prices of specialty drugs have prompted a debate about how medications are priced. With the average price of cancer drugs doubling in the last decade, the unsustainability of drug prices is especially concerning in oncology and hematology. The objective of this study was to compare the prices of monoclonal antibodies (mAbs) approved in the last 20 years by the FDA across disease states. STUDY DESIGN: We identified all indications approved by the FDA for mAbs from 1997 to 2016 and calculated the annual price of 1-year treatment for each mAb-indication combination as the product of the US average wholesale price per milligram and the recommended dose...
February 2018: American Journal of Managed Care
Vivek Subbiah, Razelle Kurzrock
The pace of genomic and immunological breakthroughs in oncology is accelerating, making it likely that large randomized trials will increasingly become outdated before their completion. Traditional clinical research/practice paradigms must adapt to the reality unveiled by genomics, especially the need for customized drug combinations, rather than one-size-fits-all monotherapy. The raison-d'être of precision oncology is to offer 'the right drug for the right patient at the right time', a process enabled by transformative tissue and blood-based genomic technologies...
February 2018: Trends in Cancer
Jeremiah D Farelli, Kirtika H Asrani, Cleo Isaacs, Joanna S deBear, Mary R Stahley, Anumeha Shah, Melissa A Lasaro, Christopher J Cheng, Romesh R Subramanian
Messenger RNA (mRNA) is a promising new class of therapeutics that has potential for treatment of diseases in fields such as immunology, oncology, vaccines, and inborn errors of metabolism. mRNA therapy has several advantages over DNA-based gene therapy, including the lack of the need for nuclear import and transcription, as well as limited possibility of genomic integration. One drawback of mRNA therapy, especially in cases such as metabolic disorders where repeated dosing will be necessary, is the relatively short in vivo half-life of mRNA (∼6-12 h)...
February 13, 2018: Nucleic Acid Therapeutics
B Allard, S Aspeslagh, S Garaud, F A Dupont, C Solinas, M Kok, B Routy, C Sotiriou, J Stagg, L Buisseret
Cancer immunotherapy is demonstrating impressive clinical benefit in different malignancies and clinical oncologists are increasingly turning their attention to immune-oncology. It is now well recognized that innate and adaptive immune cells infiltrating tumors are associated with clinical outcomes and responses to treatments, and can be harnessed to patients' benefit. Considerable advances have also been made in understanding how cancers escape from immune attack. Targeting of immunological escape processes regulated by the expression of immune checkpoint receptors and ligands and the down-modulation of tumor antigen presentation is the basis of immuno-oncology treatments...
February 8, 2018: Seminars in Cancer Biology
Sylvie Delhalle, Sebastian F N Bode, Rudi Balling, Markus Ollert, Feng Q He
Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tumor cells show a much higher degree of complexity in heterogeneity, dynamics, memory-capability, plasticity and "social" interactions. There is still a long way ahead on translating our capability to identify potentially targetable personalized biomarkers into effective personalized therapy in immune-centralized diseases...
2018: NPJ Systems Biology and Applications
Maria Margarete Karsten, Sabine Enders, Julia Knabl, Verena Kirn, Peter Düwell, Brigitte Rack, Jens-Uwe Blohmer, Doris Mayr, Darius Dian
PURPOSE: In 2005, Breuing et al. first described the use of acellular dermal matrices (ADMs) in breast cancer patients. ADMs are assumed to be safe to use in an oncologic setting, but data from controlled studies are still needed. Here, we investigate the effects of ADMs on the production of interleukin (IL)-6 and IL-12, key regulators of immune suppression and activation. METHODS: Strattice (ST), CollaMend (CM), and Biodesign (BD) biologic meshes and TiLoop, a synthetic mesh (TL), were used in this study...
February 7, 2018: Archives of Gynecology and Obstetrics
Christophoros Astaras, Rita de Micheli, Bianca Moura, Thomas Hundsberger, Andreas F Hottinger
PURPOSE OF REVIEW: Immune checkpoint inhibitors represent a major step forward in the field of oncologic immunotherapy these last years and have significantly increased survival of cancer patients in an ever-growing number of indications. These agents block specific immune checkpoint molecules (programmed cell death protein 1 and its ligand as well as cytotoxic T-lymphocyte-associated antigen 4) that normally downregulate the immune response. These new agents show a specific range of adverse effects induced by abnormal immunologic activation...
February 1, 2018: Current Neurology and Neuroscience Reports
Rudinei Diogo Marques Linck, Rômulo Leopoldo de Paula Costa, Bernardo Garicochea
The stimulation of the immune system, in order to generate an attack against cancer cells, similarly to that which occurs in infectious disease, has long been matter of interest in oncology; however, only limited success has been achieved, with different treatment strategies tested in recent years. The development of new immune checkpoint inhibitors is currently changing this scenario, and immunotherapy is becoming a real choice among traditional cytotoxic treatments to fight cancer. Recent reports have shown efficacy and safety with the use of pembrolizumab, nivolumab, and ipilimumab for the treatment of different neoplasms, especially melanoma...
November 2017: Anais Brasileiros de Dermatologia
Kirsten E Diggins, Jocelyn S Gandelman, Caroline E Roe, Jonathan M Irish
Multiplexed single-cell experimental techniques like mass cytometry measure 40 or more features and enable deep characterization of well-known and novel cell populations. However, traditional data analysis techniques rely extensively on human experts or prior knowledge, and novel machine learning algorithms may generate unexpected population groupings. Marker enrichment modeling (MEM) creates quantitative identity labels based on features enriched in a population relative to a reference. While developed for cell type analysis, MEM labels can be generated for a wide range of multidimensional data types, and MEM works effectively with output from expert analysis and diverse machine learning algorithms...
January 18, 2018: Current Protocols in Cytometry
Agata O Zych, Malgorzata Bajor, Radoslaw Zagozdzon
The idea of using the effector immune cells to specifically fight cancer has recently evolved into an exciting concept of adoptive cell therapies. Indeed, genetically engineered T cells expressing on their surface recombinant, cancer-targeted receptors have been shown to induce promising response in oncological patients. However, in addition to exogenous expression of such receptors, there is also a need for disruption of certain genes in the immune cells to achieve more potent disease-targeted actions, to produce universal chimeric antigen receptor-based therapies or to study the signaling pathways in detail...
January 17, 2018: Archivum Immunologiae et Therapiae Experimentalis
Syril Keena T Que, Fiona O Zwald, Chrysalyne D Schmults
While the majority of cutaneous squamous cell carcinomas (cSCCs) can be treated surgically, the additional work-up and treatments indicated for high-risk cSCC remain undefined. In recent years, improvements in tumor staging systems have allowed for the more accurate stratification of tumors into high- and low-risk categories. This insight, along with the publication of cSCC guidelines, brings us closer to the development of a consensus approach. The second article in this continuing medical education series addresses in question and answer format the most common questions related to advanced and high-stage cSCCs, with a simplified flowchart...
February 2018: Journal of the American Academy of Dermatology
Chi Young Jung, Scott J Antonia
Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer...
January 2018: Tuberculosis and Respiratory Diseases
Russell W Jenkins, David A Barbie, Keith T Flaherty
Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI...
January 2018: British Journal of Cancer
Scott F Gilbert
Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated...
December 2017: PLoS Biology
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