Chimeric antigen receptors: driving immunology towards synthetic biology.
Abstract The advent of second generation chimeric antigen receptors and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naïve, central memory or stem cell-like memory T cells,...
Source: Current Opinion in Immunology - June 30, 2016 Category: Allergy & Immunology Authors: Sadelain M Tags: Curr Opin Immunol Source Type: research

High-throughput genomic profiling of tumor-infiltrating leukocytes.
Abstract 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. However, advances in genome-wide ...
Source: Current Opinion in Immunology - June 30, 2016 Category: Allergy & Immunology Authors: Newman AM, Alizadeh AA Tags: Curr Opin Immunol Source Type: research

Innate immunity against hepatitis C virus.
Abstract Hepatitis C virus (HCV) infection tends persistent and causes chronic liver diseases, including inflammation, cirrhosis and hepatocellular carcinoma. Innate immune responses triggered by HCV infection, particularly the production of interferons and pro-inflammatory cytokines, shape the early host antiviral defense, and orchestrate subsequent HCV-specific adaptive immunity. Host has evolved multifaceted means to sense HCV infection to induce innate immune responses, whereas HCV has also developed elaborate strategies to evade immune attack. Recent studies in the field have provided many new insights into t...
Source: Current Opinion in Immunology - June 28, 2016 Category: Allergy & Immunology Authors: Xu Y, Zhong J Tags: Curr Opin Immunol Source Type: research

Epitope-focused vaccine design against influenza A and B viruses.
Abstract The threat of influenza A and B variants via antigenic drift and emerging novel influenza A and B strains in the human population via antigenic shift has spurred research efforts to improve upon current seasonal influenza vaccines. In recent years, a wave of novel technological breakthroughs has lead to the identification of many broadly anti-influenza hemagglutinin (HA) monoclonal antibodies (mAbs) and the elucidation of the conserved epitopes recognized by these mAbs in both the head and the stem of HA as well as the mechanisms of inhibition. These discoveries along with an improved understanding of how...
Source: Current Opinion in Immunology - June 22, 2016 Category: Allergy & Immunology Authors: Ren H, Zhou P Tags: Curr Opin Immunol Source Type: research

Antibody-guided vaccine design: identification of protective epitopes.
i D Abstract In the last decade, progress in the analysis of the human immune response and in the isolation of human monoclonal antibodies have provided an innovative approach to the identification of protective antigens which are the basis for the design of vaccines capable of eliciting effective B-cell immunity. In this review we illustrate, with relevant examples, the power of this approach that can rapidly lead to the identification of protective antigens in complex pathogens, such as human cytomegalovirus and Plasmodium falciparum, and of conserved sites in highly variable antigens, such as influenza hemagglu...
Source: Current Opinion in Immunology - June 22, 2016 Category: Allergy & Immunology Authors: Lanzavecchia A, Frühwirth A, Perez L, Corti D Tags: Curr Opin Immunol Source Type: research

Toll-like receptor 2 in host defense against Mycobacterium tuberculosis: to be or not to be-that is the question.
Abstract Toll-like receptor (TLR) 2 is expressed on immune cells and respiratory epithelial cells lining the lung. TLR2 is not critical for protection during acute Mycobacterium tuberculosis (Mtb) infection but it has a significant multi-faceted role in containing chronic infection. This review highlights the contribution of TLR2 to host protection, immune evasion by Mtb and immune regulation during chronic Mtb infection. The TLR2-triggered pro-inflammatory cytokines initiate protective mechanisms and limit Mtb replication while the immune evasion pathways counterattack anti-bacterial effector mechanisms. The immu...
Source: Current Opinion in Immunology - June 18, 2016 Category: Allergy & Immunology Authors: Gopalakrishnan A, Salgame P Tags: Curr Opin Immunol Source Type: research

Standing on three legs: antiviral activities of RIG-I against influenza viruses.
Abstract Influenza A virus (FLUAV) is a severe pathogen of humans, able to unleash epidemics and pandemics of respiratory disease. For the host to survive virus infection, it is essential to rapidly recognize the pathogen and induce the synthesis of antiviral type I interferons (IFNs). The IFN system provides a broad spectrum of sensors that respond to conserved, virus-associated molecular patterns. For FLUAV, the RNA helicase RIG-I represents the major innate immune sensor, mainly binding and reacting to the 5' triphosphate dsRNA 'panhandle' that is formed by the conserved 5' and 3' end sequences of the viral ssR...
Source: Current Opinion in Immunology - June 16, 2016 Category: Allergy & Immunology Authors: Weber-Gerlach M, Weber F Tags: Curr Opin Immunol Source Type: research

Genetic screens to study the immune system in cancer.
Abstract RNA interference and CRISPR/Cas9 technologies now enable systematic discovery of genes that regulate key pathways in the complex interaction between immune cells and tumor cells. Discovery screens are feasible in an in vivo setting, allowing identification of genes that limit the effectiveness of anti-tumor immunity. In vivo discovery screens can be informed by single-cell RNA-seq experiments that define the differentially expressed genes between functionally distinct immune cell subpopulations, both in humans and relevant animal models. Novel targets for cancer immunotherapy are being defined by the in d...
Source: Current Opinion in Immunology - June 13, 2016 Category: Allergy & Immunology Authors: Wucherpfennig KW, Cartwright AN Tags: Curr Opin Immunol Source Type: research

Antigenic landscape of the HIV-1 envelope and new immunological concepts defined by HIV-1 broadly neutralizing antibodies.
Abstract The isolation of HIV-1 broadly neutralizing antibodies (bnAbs) has demonstrated the ability of the human immune system to mount effective antibody responses against the virus. To harness this immune potential to elicit similar antibody responses by vaccination, it is important to understand the immunological processes that produce them. Here we review recent advances in crystal structural determinations of HIV-1 bnAb epitopes that directly portray the antigenic landscape of the HIV-1 envelope glycoprotein. We also summarize new immunological concepts implicated in bnAb sequences and their lineage studies....
Source: Current Opinion in Immunology - June 9, 2016 Category: Allergy & Immunology Authors: Wu X, Kong XP Tags: Curr Opin Immunol Source Type: research

Challenges and strategies for the eradication of the HIV reservoir.
Abstract Despite the success of highly active antiretroviral therapy (HAART) for inhibiting HIV replication and improving clinical outcomes, it fails to cure infection due to the existence of a stable latent proviral reservoir in memory CD4(+) T cells. Because of the longevity of these cells harboring transcriptionally silent proviruses, devising strategies to induce viral gene expression so the host immune response can mediate clearance of the infected cells or the cells can undergo virus-induced cell death, has been of considerable recent interest. Here, we review current knowledge of latency, and the challenges...
Source: Current Opinion in Immunology - June 8, 2016 Category: Allergy & Immunology Authors: Kimata JT, Rice AP, Wang J Tags: Curr Opin Immunol Source Type: research

Viral vectors as vaccine platforms: from immunogenicity to impact.
Abstract Viral vectors are the vaccine platform of choice for many pathogens that have thwarted efforts towards control using conventional vaccine approaches. Although the STEP trial encumbered development of recombinant human adenovirus vectors only a few years ago, replication-deficient simian adenoviruses have since emerged as a crucial component of clinically effective prime-boost regimens. The vectors discussed here elicit functionally relevant cellular and humoral immune responses, at extremes of age and in diverse populations. The recent Ebola virus outbreak highlighted the utility of viral vectored vaccine...
Source: Current Opinion in Immunology - June 7, 2016 Category: Allergy & Immunology Authors: Ewer KJ, Lambe T, Rollier CS, Spencer AJ, Hill AV, Dorrell L Tags: Curr Opin Immunol Source Type: research

Heads, stalks and everything else: how can antibodies eradicate influenza as a human disease?
Abstract Current seasonal influenza virus vaccines are effective against infection but they have to be reformulated on a regular basis to counter antigenic variations. The majority of the antibodies induced in response to seasonal vaccination are strain-specific. However, antibodies targeting conserved epitopes on the hemagglutinin protein have been identified and they offer broad protection. Most of these antibodies bind the hemagglutinin stalk domain and are generated from preexisting memory B cells. Broadly protective stalk-biased responses induced by antigenically divergent influenza strains, in concert with p...
Source: Current Opinion in Immunology - June 3, 2016 Category: Allergy & Immunology Authors: Neu KE, Henry Dunand CJ, Wilson PC Tags: Curr Opin Immunol Source Type: research

New concepts in HIV-1 vaccine development.
Abstract With 2 million people newly infected with HIV-1 in 2014, an effective HIV-1 vaccine remains a major public health priority. HIV-1 vaccine efficacy trials in humans, complemented by active and passive immunization studies in non-human primates, have identified several key vaccine-induced immunological responses that may correlate with protection against HIV-1 infection. Potential correlates of protection in these studies include V2-specific, polyfunctional, and broadly neutralizing antibody responses, as well as effector memory T cell responses. Here we review how these correlates of protection are guiding...
Source: Current Opinion in Immunology - June 3, 2016 Category: Allergy & Immunology Authors: Stephenson KE, D'Couto HT, Barouch DH Tags: Curr Opin Immunol Source Type: research

Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions.
Abstract It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA-B*57:01(+) individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define ...
Source: Current Opinion in Immunology - June 1, 2016 Category: Allergy & Immunology Authors: Illing PT, Mifsud NA, Purcell AW Tags: Curr Opin Immunol Source Type: research

Genomic determinants of cancer immunotherapy.
Abstract Cancer immunotherapies - including therapeutic vaccines, adoptive cell transfer, oncolytic viruses, and immune checkpoint blockade - yield durable responses in many cancer types, but understanding of predictors of response is incomplete. Genomic characterization of human cancers has already contributed to the success of targeted therapies; in cancer immunotherapy, identification of tumor-specific antigens through whole-exome sequencing may be key to designing individualized, highly immunogenic therapeutic vaccines. Additionally, pre-treatment tumor mutational and gene expression signatures can predict whi...
Source: Current Opinion in Immunology - May 30, 2016 Category: Allergy & Immunology Authors: Miao D, Van Allen EM Tags: Curr Opin Immunol Source Type: research

Childhood allergies and asthma: New insights on environmental exposures and local immunity at the lung barrier.
Abstract While certain bacteria and respiratory viruses promote local inflammation and disease onset, a more diverse colonization of the different species in the (gut) microbiome may be linked to more regulatory responses and protection against asthma and allergies. These processes are also influenced in part by food intake, both targeting the composition of the gut microbiome and influencing the immune system via metabolites. Early life environmental microbial exposure also contributes to protection against asthma and allergy and is linked with an early activation of the innate immune system and the development o...
Source: Current Opinion in Immunology - May 30, 2016 Category: Allergy & Immunology Authors: Smits HH, van der Vlugt LE, von Mutius E, Hiemstra PS Tags: Curr Opin Immunol Source Type: research

Monitoring immune responses in the tumor microenvironment.
Abstract Immune monitoring in the tumor microenvironment allows for important insights into immune mechanisms of response and resistance to various cancer treatments; however clinical challenges exist using current strategies. Significant questions remain regarding monitoring of archival versus fresh tissue, assessment of static versus dynamic markers, evaluation of limited tissue samples, and the translation of insights gained from immunologically 'hot' tumors such as melanoma to other 'cold' tumor microenvironments prevalent in other cancer types. Current and emerging immune monitoring strategies will be examine...
Source: Current Opinion in Immunology - May 27, 2016 Category: Allergy & Immunology Authors: Wargo JA, Reddy SM, Reuben A, Sharma P Tags: Curr Opin Immunol Source Type: research

Recent innovations in mRNA vaccines.
Abstract Nucleic acid-based vaccines are being developed as a means to combine the positive attributes of both live-attenuated and subunit vaccines. Viral vectors and plasmid DNA vaccines have been extensively evaluated in human clinical trials and have been shown to be safe and immunogenic, although none have yet been licensed for human use. Recently, mRNA based vaccines have emerged as an alternative approach. They promise the flexibility of plasmid DNA vaccines, without the need for electroporation, but with enhanced immunogenicity and safety. In addition, they avoid the limitations of anti-vector immunity seen...
Source: Current Opinion in Immunology - May 26, 2016 Category: Allergy & Immunology Authors: Ulmer JB, Geall AJ Tags: Curr Opin Immunol Source Type: research

Interplay of innate and adaptive immunity in metal-induced hypersensitivity.
Abstract Metal-induced hypersensitivity is driven by T cell sensitization to metal ions. Recent advances in our understanding of the complex interactions between innate and adaptive immunity have expanded our knowledge of the pathogenesis of these diseases. Metals activate the innate immune system through direct binding to pathogen recognition receptors, activation of the inflammasome, or the induction of cellular death and release of alarmins. Certain metals can serve as adjuvants, promoting dendritic cell activation and migration as well as antigen presentation to metal-specific T cells. These T cells can recogn...
Source: Current Opinion in Immunology - May 23, 2016 Category: Allergy & Immunology Authors: McKee AS, Fontenot AP Tags: Curr Opin Immunol Source Type: research

Epigenetic modifications: mechanisms of disease and biomarkers of food allergy.
Abstract The rise in IgE-mediated food allergy in recent times is the likely result of gene-environment interactions mediated via epigenetic pathways. As epigenetic modifications, including DNA methylation, are at the interface between the environment and the genome, they may be ideal biomarkers of modifiable disease pathways. High-throughput methylation profiling of immune cell subtypes or whole blood from patients allows the identification of disease specific epigenetic variants. If faithfully tracking with disease parameters, these 'signatures' may have clinical applications as biomarkers of disease or therapeu...
Source: Current Opinion in Immunology - May 21, 2016 Category: Allergy & Immunology Authors: Martino DJ, Saffery R, Allen KJ, Prescott SL Tags: Curr Opin Immunol Source Type: research

Atopic dermatitis and filaggrin.
Abstract Filaggrin has a key structural and functional role in the epidermis with important impact on the homeostasis of the skin. Inherited or acquired filaggrin deficiency has been described to essentially contribute to the pathogenesis of atopic dermatitis (AD), one of the most frequent chronic eczematous skin diseases in child-hood and adult-hood. Increasing knowledge has been gained during the last years about direct and indirect consequences of filaggrin deficiency. Furthermore, with the help of novel murine and human experimental models important steps forward have been made towards the characterization of ...
Source: Current Opinion in Immunology - May 17, 2016 Category: Allergy & Immunology Authors: Cabanillas B, Novak N Tags: Curr Opin Immunol Source Type: research

Editorial overview: Antigen processing.
PMID: 27178764 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - May 10, 2016 Category: Allergy & Immunology Authors: Norbury CC, Eisenlohr LC Tags: Curr Opin Immunol Source Type: research

Mass spectrometry-based antigen discovery for cancer immunotherapy.
Abstract The antigenic landscape of tumors is distinct from healthy cells and has been the rationale behind a variety of vaccination trials. Typically the target tumor-associated antigens have been of self origin and have rarely induced effective anti-tumor responses. Recent data show that activation of the immune system by immune checkpoint blocking therapies leads to tumor rejection and that recognition of mutated antigens, known as 'neo-antigens' plays a key role. Discovery of neo-antigens relies mainly on prediction-based interrogation of the 'mutanome' using genomic information as input, followed by T-cell sc...
Source: Current Opinion in Immunology - May 4, 2016 Category: Allergy & Immunology Authors: Bassani-Sternberg M, Coukos G Tags: Curr Opin Immunol Source Type: research

Giving CD4+ T cells the slip: viral interference with MHC class II-restricted antigen processing and presentation.
Abstract Activation of CD4+ T cells through interactions with peptides bound to Major Histocompatibility Complex Class II (MHC-II) molecules is a crucial step in clearance of most pathogens. Consequently, many viruses have evolved ways of blocking this aspect of adaptive immunity, from specific targeting of processing and presentation components to modulation of signaling pathways that regulate peptide presentation in addition to many other host defense mechanisms. Such cases of interference are far less common compared to what has been elucidated in MHC-I processing and presentation. This may be attributable in p...
Source: Current Opinion in Immunology - April 23, 2016 Category: Allergy & Immunology Authors: Forsyth KS, Eisenlohr LC Tags: Curr Opin Immunol Source Type: research

Vaccination in early life: standing up to the challenges.
Abstract The challenge for any vaccine design is to elicit protective humoral and/or cytotoxic immunity against life threatening pathogens while remaining innocuous. Neonatal vaccinology faces additional challenges linked to intrinsic peculiarities of the innate and adaptive neonatal immune system. These include anti-inflammatory rather than pro-inflammatory responses to innate signals, preferential Th2 differentiation limiting the induction of Th1 and cytotoxic responses, trends to immunoregulatory responses and weak plasma cell and germinal centre B cell responses. Recent progresses in our understanding of the m...
Source: Current Opinion in Immunology - April 19, 2016 Category: Allergy & Immunology Authors: Mohr E, Siegrist CA Tags: Curr Opin Immunol Source Type: research

The source of MHC class I presented peptides and its implications.
us R Abstract The source of peptides that enter the major histocompatibility class I (MHCI) pathway has been intensively debated over the last two decades. The initial assumption that peptides are derived from degradation of full length proteins was challenged by a model in which alternative translation products are a source of peptides. This model has been tested and supported by scientific data. We now need new hypotheses on the physiological implications of different sources of peptides for the MHCI pathway. The aim of this overview is to give an up-to-date account of the source of antigenic peptide material fo...
Source: Current Opinion in Immunology - April 19, 2016 Category: Allergy & Immunology Authors: Apcher S, Prado Martins R, Fåhraeus R Tags: Curr Opin Immunol Source Type: research

Defining cross presentation for a wider audience.
Abstract Cross presentation is the process of production of peptide-MHC Class I complexes by cells in which the antigen that is the source of peptide is not translated. The majority of recent studies have described many facets of the classical TAP-dependent cross presentation pathway, but numerous pathways for transfer of antigenic material from a donor to a recipient cell followed by subsequent MHC-I-restricted presentation have been established, including transfer of protein antigen, peptide, RNA, DNA or even peptide-MHC-I complexes. The extent to which each of these pathways generates overlapping or unique pept...
Source: Current Opinion in Immunology - April 18, 2016 Category: Allergy & Immunology Authors: Norbury CC Tags: Curr Opin Immunol Source Type: research

Editorial overview: Special section: New concepts in antibody therapeutics: What's in store for antibody therapy?
PMID: 27083411 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - April 12, 2016 Category: Allergy & Immunology Authors: Schuurman J, Parren PW Tags: Curr Opin Immunol Source Type: research

Recent advances in viral evasion of the MHC Class I processing pathway.
Abstract T-cell mediated adaptive immunity against viruses relies on recognition of virus-derived peptides by CD4(+) and CD8(+) T cells. Detection of pathogen-derived peptide-MHC-I complexes triggers CD8(+) T cells to eliminate the infected cells. Viruses have evolved several mechanisms to avoid recognition, many of which target the MHC-I antigen-processing pathway. While many immune evasion strategies have been described in the context of herpesvirus infections, it is becoming clear that this 'disguise' ability is more widespread. Here, we address recent findings in viral evasion of the MHC-I antigen presentation...
Source: Current Opinion in Immunology - April 8, 2016 Category: Allergy & Immunology Authors: Schuren AB, Costa AI, Wiertz EJ Tags: Curr Opin Immunol Source Type: research

Deep sequencing and human antibody repertoire analysis.
Abstract In the past decade, high-throughput DNA sequencing (HTS) methods and improved approaches for isolating antigen-specific B cells and their antibody genes have been applied in many areas of human immunology. This work has greatly increased our understanding of human antibody repertoires and the specific clones responsible for protective immunity or immune-mediated pathogenesis. Although the principles underlying selection of individual B cell clones in the intact immune system are still under investigation, the combination of more powerful genetic tracking of antibody lineage development and functional test...
Source: Current Opinion in Immunology - April 8, 2016 Category: Allergy & Immunology Authors: Boyd SD, Crowe JE Tags: Curr Opin Immunol Source Type: research

Immunology by numbers: quantitation of antigen presentation completes the quantitative milieu of systems immunology!
Abstract We review approaches to quantitate antigen presentation using a variety of biological and biochemical readouts and highlight the emerging role of mass spectrometry (MS) in defining and quantifying MHC-bound peptides presented at the cell surface. The combination of high mass accuracy in the determination of the molecular weight of the intact peptide of interest and its signature pattern of fragmentation during tandem MS provide an unambiguous and definitive identification. This is in contrast to the potential receptor cross-reactivity towards closely related peptides and variable dose responsiveness seen ...
Source: Current Opinion in Immunology - April 6, 2016 Category: Allergy & Immunology Authors: Purcell AW, Croft NP, Tscharke DC Tags: Curr Opin Immunol Source Type: research

Immunocytokines for cancer treatment: past, present and future.
Abstract Immunocytokines are antibody-cytokine fusion proteins, with the potential to preferentially localize on tumor lesions and to activate anticancer immunity at the site of disease. Various tumor targets (e.g., cell membrane antigens and extracellular matrix components) and antibody formats (e.g., intact IgG and antibody fragments) have been considered for immunocytokine development and some products have advanced to clinical trials. In this review, we present relevant concepts and strategies for the design and use of anticancer immunocytokine products. In addition, we discuss emerging strategies for the phar...
Source: Current Opinion in Immunology - April 6, 2016 Category: Allergy & Immunology Authors: Neri D, Sondel PM Tags: Curr Opin Immunol Source Type: research

Harnessing Fc receptor biology in the design of therapeutic antibodies.
Abstract The antibody Fc domain engages the small family of Fc receptors, expressed on cells of the immune system and beyond, to stimulate a rich diversity of positive and negative cell-mediated effector functions. The emergence of monoclonal antibodies for the treatment of various pathologic conditions has provided additional insights into Fc receptor biology, and has suggested new strategies to exploit Fc receptor interactions to create improved therapeutics. While most therapeutic IgGs approved to date have retained a native IgG Fc domain, the knowledge gained over the last decades has provided the opportunity ...
Source: Current Opinion in Immunology - March 30, 2016 Category: Allergy & Immunology Authors: Sondermann P, Szymkowski DE Tags: Curr Opin Immunol Source Type: research

The melting pot of the MHC II peptidome.
Abstract Recent advances in mass spectrometry technology have facilitated detailed examination of MHC-II immunopeptidomes, for example the repertoires of peptides bound to MHC-II molecules expressed in antigen presenting cells. These studies have deepened our view of MHC-II presentation. Other studies have broadened our view of pathways leading up to peptide loading. Here we review these recent studies in the context of earlier work on conventional and non-conventional MHC-II processing. The message that emerges is that sources of antigen beyond conventional endosomal processing of endocytosed proteins are importa...
Source: Current Opinion in Immunology - March 25, 2016 Category: Allergy & Immunology Authors: Stern LJ, Santambrogio L Tags: Curr Opin Immunol Source Type: research

Immunoglobulin isotype knowledge and application to Fc engineering.
Abstract Monoclonal antibody-based drugs continue to be one of the most rapidly growing classes of therapeutic molecules. At present, the majority of approved therapeutic antibodies are of the human IgG1 format, which can elicit immune effector functions (e.g., antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity). However, there is a wealth of functional diversity that is present in other isotypes and IgG subclasses that can be exploited to improve clinical safety and performance by increasing stability, reduction of adverse events, modulation o...
Source: Current Opinion in Immunology - March 19, 2016 Category: Allergy & Immunology Authors: Brezski RJ, Georgiou G Tags: Curr Opin Immunol Source Type: research

Promises and pitfalls for recombinant oligoclonal antibodies-based therapeutics in cancer and infectious disease.
Abstract Monoclonal antibodies (mAbs) have revolutionized the diagnosis and treatment of many human diseases and the application of combinations of mAbs has demonstrated improved therapeutic activity in both preclinical and clinical testing. Combinations of antibodies have several advantages such as the capacities to target multiple and mutating antigens in complex pathogens and to engage varied epitopes on multiple disease-related antigens (e.g. receptors) to overcome heterogeneity and plasticity. Oligoclonal antibodies are an emerging therapeutic format in which a novel antibody combination is developed as a sin...
Source: Current Opinion in Immunology - March 17, 2016 Category: Allergy & Immunology Authors: Corti D, Kearns JD Tags: Curr Opin Immunol Source Type: research

Staying local-antigen presentation in the liver.
Abstract The liver is known as organ with unique immune competence. Besides its unique microenvironment that is determined by gut-derived portal venous blood constituents and the presence of enzymes with immune regulatory properties, liver antigen presenting cell populations regulate antigen-specific immunity in a local fashion. In addition to bone marrow-derived dendritic cells and myeloid cells such as macrophages and monocytes, also truly liver-resident cell populations function as antigen presenting cells such as liver sinusoidal endothelial cells and hepatocytes. The functional outcome of antigen-presentation...
Source: Current Opinion in Immunology - March 11, 2016 Category: Allergy & Immunology Authors: Knolle PA Tags: Curr Opin Immunol Source Type: research

Disentangling the relationship between tumor genetic programs and immune responsiveness.
Abstract Correlative studies in humans have demonstrated that an active immune microenvironment characterized by the presence of a T-helper 1 immune response typifies a tumor phenotype associated with better outcome and increased responsiveness to immune manipulation. This phenotype also signifies the counter activation of immune-regulatory mechanisms. Variables modulating the development of an effective anti-tumor immune response are increasingly scrutinized as potential therapeutic targets. Genetic alterations of cancer cells that functionally influence intratumoral immune response include mutational load, speci...
Source: Current Opinion in Immunology - March 8, 2016 Category: Allergy & Immunology Authors: Bedognetti D, Hendrickx W, Ceccarelli M, Miller LD, Seliger B Tags: Curr Opin Immunol Source Type: research

New developments for antibody-drug conjugate-based therapeutic approaches.
Abstract The clinical success of Adcetris(®) (brentuximab vedotin) and Kadcyla(®) (ado-trastuzumab emtansine) has sparked clinical development of novel ADCs. These powerful anti-cancer agents are designed to allow specific targeting of highly potent cytotoxic agents to tumor cells while sparing healthy tissues. Despite the use of tumor-specific antibodies, the emerging clinical data with ADCs indicates that adverse effects frequently occur before ADCs have reached their optimal therapeutic dose, resulting in a relatively narrow therapeutic window. This review summarizes the therapeutic window of ADCs curre...
Source: Current Opinion in Immunology - March 7, 2016 Category: Allergy & Immunology Authors: de Goeij BE, Lambert JM Tags: Curr Opin Immunol Source Type: research

Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection.
Abstract To realize the full potential of cancer immunotherapy, the latest generation immunotherapeutics are designed to harness the potent tumor-killing capacity of T cells. Thus, to mobilize T cells, new optimized bispecific antibody (BsAb) designs, enabling efficient polyclonal redirection of cytotoxic activity through binding to CD3 and a Tumor Associated Antigen (TAA) and refined genetically modified T cells have recently expanded the arsenal of available options for cancer treatment. This review presents the current understanding of the parameters crucial to the design of optimal T cell redirecting BsAb and ...
Source: Current Opinion in Immunology - March 7, 2016 Category: Allergy & Immunology Authors: Zhukovsky EA, Morse RJ, Maus MV Tags: Curr Opin Immunol Source Type: research

Polarity and asymmetric cell division in the control of lymphocyte fate decisions and function.
Abstract Polarity is important in several lymphocyte processes including lymphocyte migration, formation of the immunological synapse, and asymmetric cell division (ACD). While lymphocyte migration and immunological synapse formation are relatively well understood, the role of lymphocyte ACD is less clear. Recent advances in measuring polarity enable more robust analyses of asymmetric cell division. Use of these new methods has produced crucial quantification of ACD at precise phases of lymphocyte development and activation. These developments are leading to a better understanding of the drivers of fate choice dur...
Source: Current Opinion in Immunology - March 2, 2016 Category: Allergy & Immunology Authors: Yassin M, Russell SM Tags: Curr Opin Immunol Source Type: research

Editorial overview: Lymphocyte development and activation: Lymphoid cell differentiation: choosing paths to traverse the immune landscape.
PMID: 26923180 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - February 25, 2016 Category: Allergy & Immunology Authors: Hagman J Tags: Curr Opin Immunol Source Type: research

Editorial overview: Tumour immunology: What's beyond today's success in tumor immunology.
PMID: 26905641 [PubMed - as supplied by publisher] (Source: Current Opinion in Immunology)
Source: Current Opinion in Immunology - February 20, 2016 Category: Allergy & Immunology Authors: van der Burg SH, Marincola F Tags: Curr Opin Immunol Source Type: research

Orchestration of B lymphoid cells and their inner myeloid by Bach.
Abstract The transcription repressor Bach2 is required for class switch recombination and somatic hypermutation of antibody genes in B cells, and proper development of effector and regulatory T cells. In addition, Bach2 and its related factor Bach1 promote B cell commitment of progenitor cells by repressing myeloid-related genes. Bach2 and the myeloid regulators C/EBPβ and C/EBPα mutually repress their expression, forming a gene regulatory network (GRN) that dictates the process of lineage commitment. Bach2 forms another GRN with the plasma cell regulator Blimp-1, in which Bach2 and Blimp-1 mutually rep...
Source: Current Opinion in Immunology - February 16, 2016 Category: Allergy & Immunology Authors: Igarashi K, Itoh-Nakadai A Tags: Curr Opin Immunol Source Type: research

Regulation of T cell signaling and autoimmunity by RNA-binding proteins.
Abstract Post-transcriptional gene regulation by RNA-binding proteins controls mRNA half-life and efficiency of translation. Recently, the RNA-binding proteins Roquin and Regnase-1 have been shown to play pivotal roles in T lymphocytes by preventing inflammatory and autoimmune disease. These factors share an overlapping set of target mRNAs and are both regulated by proteolytic cleavage through the paracaspase MALT1. This review discusses the mouse models of inactivation or deregulation and how these trans-acting factors recognize target mRNAs. Based on different affinities of cis-elements in target mRNAs and regul...
Source: Current Opinion in Immunology - February 9, 2016 Category: Allergy & Immunology Authors: Jeltsch KM, Heissmeyer V Tags: Curr Opin Immunol Source Type: research

The development of adult innate lymphoid cells.
Abstract Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence...
Source: Current Opinion in Immunology - February 4, 2016 Category: Allergy & Immunology Authors: Yang Q, Bhandoola A Tags: Curr Opin Immunol Source Type: research

Exploring the multifaceted nature of the common lymphoid progenitor compartment.
Abstract While the common lymphoid progenitor compartment was originally thought to be a rather homogenous cell population, it has become increasingly clear that this compartment is highly heterogeneous both with regard to phenotypic and functional features. The exploration of this cellular complexity has generated novel molecular insights into regulatory events in lymphoid lineage restriction and provided support for the idea that multiple lineage restriction events occur at this developmental stage. Furthermore, the identification of multiple lineage-restricted progenitors with mixed lineage potential challenges...
Source: Current Opinion in Immunology - February 4, 2016 Category: Allergy & Immunology Authors: Jensen CT, Strid T, Sigvardsson M Tags: Curr Opin Immunol Source Type: research

Combinatorial immunotherapy strategies for hepatocellular carcinoma.
Abstract Hepatocellular carcinoma (HCC) is the most common liver malignancy. The prognosis for HCC patients greatly varies according to the stage at diagnosis. Overall it is poor, with a 5-year survival rate of approximately 5-6%. Immunotherapeutic interventions represent a novel and effective therapeutic tool. However, only few immunotherapy trials for HCC have been conducted so far with contrasting results, suggesting that significant improvements are needed. Indeed, the liver is characterized by a strong intrinsic immune suppressive microenvironment which needs to be counterbalanced with immune stimulatory appr...
Source: Current Opinion in Immunology - February 3, 2016 Category: Allergy & Immunology Authors: Tagliamonte M, Petrizzo A, Tornesello ML, Ciliberto G, Buonaguro FM, Buonaguro L Tags: Curr Opin Immunol Source Type: research

Development and maturation of natural killer cells.
Abstract Natural killer (NK) cells are innate lymphocytes that are critical for host protection against pathogens and cancer due to their ability to rapidly release inflammatory cytokines and kill infected or transformed cells. In the 40 years since their initial discovery, much has been learned about how this important cellular lineage develops and functions. We now know that NK cells are the founding members of an expanded family of lymphocyte known as innate lymphoid cells (ILC). Furthermore, we have recently discovered that NK cells can possess features of adaptive immunity such as antigen specificity and long...
Source: Current Opinion in Immunology - February 1, 2016 Category: Allergy & Immunology Authors: Geiger TL, Sun JC Tags: Curr Opin Immunol Source Type: research

AID hits the jackpot when missing the target.
Abstract Activation induced deaminase is the single B cell specific factor mediating class switch recombination and somatic hypermutation. Numerous studies have shown that AID preferentially targets Ig substrates and also attacks non-Ig substrates to create DNA damage that contributes to lymphomagenesis. AID targeting to Ig loci is linked to transcription but the mechanism governing this process has been obscure. Here we discuss research that illustrates the connection between AID targeting to DNA substrates and transcription processes to reveal rules governing the specificity of AID attack. These observations are...
Source: Current Opinion in Immunology - February 1, 2016 Category: Allergy & Immunology Authors: Kenter AL, Kumar S, Wuerffel R, Grigera F Tags: Curr Opin Immunol Source Type: research