Abstract：
:The elicitation of anti-drug antibodies (ADA) against biotherapeutics can have detrimental effects on drug safety, efficacy, and pharmacokinetics. The immunogenicity of biotherapeutics is, therefore, an important issue. There is evidence that protein aggregation can result in enhanced immunogenicity; however, the precise immunological and biochemical mechanisms responsible are poorly defined. In the context of biotherapeutic drug development and safety assessment, understanding the mechanisms underlying aggregate immunogenicity is of considerable interest. This review provides an overview of the phenomenon of protein aggregation, the production of unwanted aggregates during bioprocessing, and how the immune response to aggregated protein differs from that provoked by non-aggregated protein. Of particular interest is the nature of the interaction of aggregates with the immune system and how subsequent ADA responses are induced. Pathways considered here include 'classical' activation of the immune system involving antigen presenting cells and, alternatively, the breakdown of B-cell tolerance. Additionally, methods available to screen for aggregation and immunogenicity will be described. With an increased understanding of aggregation-enhanced immune responses, it may be possible to develop improved manufacturing and screening processes to avoid, or at least reduce, the problems associated with ADA.
journal_name
J Immunotoxicoljournal_title
Journal of immunotoxicologyauthors
Ratanji KD,Derrick JP,Dearman RJ,Kimber Idoi
10.3109/1547691X.2013.821564subject
Has Abstractpub_date
2014-04-01 00:00:00pages
99-109issue
2eissn
1547-691Xissn
1547-6901journal_volume
11pub_type
杂志文章,评审abstract：:Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of the pro-inflammatory interleukin-1-mediated activation of the interleukin-1 receptor (IL-1R). Although wild-type IL-1Ra is used for treatment of inflammatory diseases, its effect is moderate and/or short-lived. The objective of this study...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910802131477
更新日期：2008-04-01 00:00:00
abstract：:The realization, that the immune system can be the target of many chemicals including environmental contaminants and drugs with potentially adverse effects on the host's health, has raised serious concerns within the public and the regulatory agencies. At present, assessment of immunotoxic effects relies on different ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章,评审
doi：10.3109/1547691X.2010.509848
更新日期：2010-10-01 00:00:00
abstract：:Among the different phenotypic changes induced by contact sensitizers in dendritic cells and myeloid cell lines, CD86 appears to be a consensus marker, since constantly described as systematically up-regulated. To evaluate the robustness of this marker, interference of cytotoxicity on CD86 expression was investigated ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910600978038
更新日期：2006-12-01 00:00:00
abstract：:In the past two decades, hematologic and immunologic disorders in humans have been increasingly reported as a result of pesticide exposures. Therefore, safety assessment is required to assess the effects on hematopoiesis and thus on the immune system in addition to routine toxicity evaluation. Currently, the data avai...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2014.880535
更新日期：2015-01-01 00:00:00
abstract：:In recent decades, in the US and in Western and Northern Europe, there has been a significant increase in the prevalence of atopic allergic disease. Although that increase may now be slowing, or have already reached a plateau, there remains considerable interest in the factor or factors that may have caused this incre...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2012.707696
更新日期：2013-04-01 00:00:00
abstract：:Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water i...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2016.1154118
更新日期：2016-09-01 00:00:00
abstract：:A number of immunomodulatory therapeutics increase the risk of disease associated with latent herpesviruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV), a member of the lymphocryptovirus (LCV) family that infects humans. The diseases associated with loss of immunity to these viruses can have major impac...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2013.766287
更新日期：2014-01-01 00:00:00
abstract：:Pulmonary infections have been reported to be increased in welders. Previous animal studies have indicated that manual metal arc, stainless steel welding fume (MMA-SS) increased susceptibility to lung infections. MMA-SS is composed of a complex of metals (e.g., iron, chromium, nickel). The objective was to determine w...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910701336953
更新日期：2007-04-01 00:00:00
abstract：:Many environmental toxins have been shown to suppress the immune system across taxa. The foreign red blood cell (RBC) challenge is an important part of a complement of tests used to assess immunocompetence in the laboratory because it can assess an individual's humoral response without impacting its health. This chall...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910903023060
更新日期：2009-09-01 00:00:00
abstract：:The influence of size of nanoparticles (NP), especially in regard to pulmonary toxicity, has been widely investigated. In general, NP with smaller diameters are more pro-inflammatory in vivo, at least in terms of neutrophil influx. Nevertheless, the influence of size of NP on polymorphonuclear neutrophil (PMN) cell bi...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2015.1106622
更新日期：2016-05-01 00:00:00
abstract：:The development of immune-dependent drug hypersensitivity reactions (IDHR) is likely to involve activation of the innate immune system to stimulate neo-antigen specific T-cells. Previously it has been shown that, upon oral exposure to several drugs with immune-adjuvant capacity, mice developed T-cell-dependent respons...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2016.1139643
更新日期：2016-07-01 00:00:00
abstract：:Use of enzymes in cosmetic products is novel and the safety of these products is not well understood. The safety of a prototype enzyme-containing body moisturizer lotion was tested via measures of skin compatibility and potential to induce protease-specific IgE antibody in a clinical study. Female, atopic subjects (n ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910490496249
更新日期：2004-04-01 00:00:00
abstract：:The present study was designed to examine and compare the effects of three suppressors on the cytokine response in tandem with examining: the synthesis of inducible forms of heat shock proteins; HSP72 and HSP90α; activities of NF-κB and SAPK/JNK signaling pathways; and TLR4 expression. Pre-treatment with inhibitors of...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2012.700652
更新日期：2013-04-01 00:00:00
abstract：:Curcumin has been found to possess anti-inflammatory activities and neutrophils, key players in inflammation, were previously found to be important targets to curcumin in a few studies. For example, curcumin was found to induce apoptosis in neutrophils by a p38 mitogen-activated protein kinase (MAPK)-dependent mechani...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2014.917749
更新日期：2015-04-01 00:00:00
abstract：:Toxicological testing of compounds often is conducted at the maximum tolerated dose to identify potential target organs. Toxicities observed at these high doses may result in decreased body weight gain, food consumption and activity. These clinical signs are often associated with a generalized stress response. It has ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910601115150
更新日期：2007-01-01 00:00:00
abstract：:Glyphosate, or N-phosphomethyl(glycine), is an organophosphorus compound and a competitive inhibitor of the shikimate pathway that allows aromatic amino acid biosynthesis in plants and microorganisms. Its utilization in broad-spectrum herbicides, such as RoundUp®, has continued to increase since 1974; glyphosate, as w...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/1547691X.2020.1804492
更新日期：2020-12-01 00:00:00
abstract：:The objective of this study was to characterize the variability of rat lymphoid organ weights and morphology following treatment with a known immunotoxicant, with a focus on the usefulness of evaluating popliteal lymph node weight and histology. Cyclophosphamide was administered to male Sprague-Dawley rats by oral gav...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2015.1122117
更新日期：2016-07-01 00:00:00
abstract：:Skeletal health consequences associated with inflammatory diseases of the airways significantly contribute to morbidity. Sex differences have been described independently for lung and bone diseases. Repetitive inhalant exposure to lipopolysaccharide (LPS) induces bone loss and deterioration in male mice, but compariso...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/1547691X.2018.1460425
更新日期：2018-12-01 00:00:00
abstract：:Here we sought to determine whether prenatal exposure to subtoxic levels of inorganic mercury induced modulations in the fetal immune repertoire. After overnight breeding of female BALB/c and male DBA/1 mice, pregnant females were exposed to 10 mg/l mercuric chloride in drinking water. DBF(1) pups were examined at day...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910701680178
更新日期：2007-10-01 00:00:00
abstract：:Indirubin-3-monoxime is an aryl hydrocarbon receptor (AhR)-binding, idole-derived compound known to be a potent inducer of CYP1A1, at least in hepatic cell lines. To date, very little is known about the effects of indirubin-3-monoxime on cells relevant to the immune system. We treated human U937 histiocytic lymphoma c...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15476910500468627
更新日期：2006-01-01 00:00:00
abstract：:Warfarin is a Vitamin K (VK) antagonist that affects Vitamin K-dependent (VKD) processes, including blood coagulation, as well as processes unrelated to hemostasis such as bone growth, calcification, and growth of some cell types. In addition, warfarin exerts influence on some non-VKD-related activities, including ant...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2012.684159
更新日期：2013-01-01 00:00:00
abstract：:Exposure to subacute ozone (O3) causes pulmonary neutrophil recruitment. In mice, this recruitment requires IL-17A. Ozone also causes expression of IL-23 and IL-1, which can induce IL-17A. The purpose of this study was to examine the hypothesis that IL-23 and IL-1 contribute to IL-17A expression and subsequent neutrop...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2015.1120829
更新日期：2016-05-01 00:00:00
abstract：:Workers exposed to benzene frequently suffer from toxicities of the bone marrow as well as the central nervous, immune, and reproductive systems. This toxicity most likely is a result of the oxidative metabolism of benzene to reactive products. As green tea possesses antioxidant effects, the objective of this study wa...
journal_title：Journal of immunotoxicology
pub_type： 临床试验,杂志文章
doi：10.1080/15476910802019029
更新日期：2008-01-01 00:00:00
abstract：:Chronic exposure to organochlorine pesticides (OCP) has been suspected of causing immunoregulatory abnormalities that eventually lead to development and progression of systemic lupus erythematosus (SLE), but the role of these non-genetic stimuli has remained poorly understood. The objectives of the study were to quant...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2011.642103
更新日期：2012-01-01 00:00:00
abstract：:Dimethyl carbonate (DMC) is an industrial chemical, used as a paint and adhesive solvent, with the potential for significant increases in production. Using select immune function assays, the purpose of these studies was to evaluate the immunotoxicity of DMC following dermal exposure using a murine model. Following a 2...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2012.691124
更新日期：2013-01-01 00:00:00
abstract：:That benzo alpha)pyrene (Balpha P) decreases both humoral and cell-mediated immunity, and leads to increases in progeny tumor development after in utero insult, suggests that T- and B-lymphocytes are made defective in exposed offspring. In the study here, C3H mice were injected once with Balpha P (150 microg/g BW) at ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/15376510802312324
更新日期：2008-07-01 00:00:00
abstract：:Transferon, a human dialyzable leukocyte extract (hDLE), is a biotherapeutic that comprises a complex mixture of low-molecular-weight peptides (< 10 kDa) and is used to treat diseases with an inflammatory component. Some biotherapeutics, including those composed of peptides, can induce anti-drug antibodies (ADA) that ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.1080/1547691X.2017.1346009
更新日期：2017-12-01 00:00:00
abstract：:The concept of immunological surveillance implies that immunogenic variants of tumor cells arising in the organism can be recognized by the immune system. Tumor progression is provided by somatic evolution of tumor cells under the pressure of the immune system. The loss of MHC Class I molecules on the surface of tumor...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2013.861548
更新日期：2014-10-01 00:00:00
abstract：:Mechanical ventilation with hyperoxia is a necessary treatment for patients with respiratory distress. However, patients on mechanical ventilation have increased susceptibility to infection. Studies including ours have shown that reactive oxygen species (ROS), generated by exposure to prolonged hyperoxia, can cause a ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2010.531063
更新日期：2011-01-01 00:00:00
abstract：:Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to play important roles in carcinogenesis. The current study was carried out to assess the possible anti-tumor effects of pioglitazone (PIO), a PPARγ agonist, in a mouse mammary carcinoma model, i.e. a solid Ehrlich carcinoma (SEC). Effects of PIO ...
journal_title：Journal of immunotoxicology
pub_type： 杂志文章
doi：10.3109/1547691X.2014.978055
更新日期：2015-01-01 00:00:00
