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Frontiers in Immunology 2019Systemic lupus erythematosus (SLE) is characterized by high-titer serological autoantibodies, including antibodies that bind to double-stranded DNA (dsDNA). The origin,... (Review)
Review
Systemic lupus erythematosus (SLE) is characterized by high-titer serological autoantibodies, including antibodies that bind to double-stranded DNA (dsDNA). The origin, specificity, and pathogenicity of anti-dsDNA antibodies have been studied from a wider perspective. These autoantibodies have been suggested to contribute to multiple end-organ injuries, especially to lupus nephritis, in patients with SLE. Moreover, serum levels of anti-DNA antibodies fluctuate with disease activity in patients with SLE. By directly binding to self-antigens or indirectly forming immune complexes, anti-dsDNA antibodies can accumulate in the glomerular and tubular basement membrane. These autoantibodies can also trigger the complement cascade, penetrate into living cells, modulate gene expression, and even induce profibrotic phenotypes of renal cells. In addition, the expression of suppressor of cytokine signaling 1 is reduced by anti-DNA antibodies simultaneously with upregulation of profibrotic genes. Anti-dsDNA antibodies may even participate in the pathogenesis of SLE by catalyzing hydrolysis of certain DNA molecules or peptides in cells. Recently, anti-dsDNA antibodies have been explored in greater depth as a therapeutic target in the management of SLE. A substantial amount of data indicates that blockade of pathogenic anti-dsDNA antibodies can prevent or even reverse organ damage in murine models of SLE. This review focuses on the recent research advances regarding the origin, specificity, classification, and pathogenicity of anti-dsDNA antibodies and highlights the emerging therapies associated with them.
Topics: Animals; Antibodies, Antinuclear; Autoantibodies; DNA; Humans; Lupus Erythematosus, Systemic; Molecular Targeted Therapy
PubMed: 31379858
DOI: 10.3389/fimmu.2019.01667 -
Drug Delivery Dec 2019ENHANZE drug delivery technology is based on the proprietary recombinant human hyaluronidase PH20 enzyme (rHuPH20; Halozyme Therapeutics, Inc.) that facilitates the... (Review)
Review
ENHANZE drug delivery technology is based on the proprietary recombinant human hyaluronidase PH20 enzyme (rHuPH20; Halozyme Therapeutics, Inc.) that facilitates the subcutaneous (SC) delivery of co-administered therapeutics. rHuPH20 works by degrading the glycosaminoglycan hyaluronan (HA), which plays a role in resistance to bulk fluid flow in the SC space, limiting large volume SC drug delivery, dispersion, and absorption. Co-administration of rHuPH20 with partner therapies can overcome administration time and volume barriers associated with existing SC therapeutic formulations, and has been shown to reduce the burden on patients and healthcare providers compared with intravenous formulations. rHuPH20 (as HYLENEX recombinant) is currently FDA-approved for subcutaneous fluid administration for achieving hydration, to increase the dispersion and absorption of other injected drugs, and in subcutaneous urography for improving resorption of radiopaque agents. rHuPH20 is also co-formulated with two anticancer therapies, trastuzumab (i.e. Herceptin SC) and rituximab (i.e. RITUXAN HYCELA/RITUXAN SC/MabThera SC) and dosed sequentially with human immunoglobin to treat primary immunodeficiency (i.e. HyQvia/HYQVIA). This article reviews pharmaceutical properties of rHuPH20, its current applications with approved therapeutics, and the potential for future developments.
Topics: Animals; Antibodies, Monoclonal; Antigens, Surface; Antineoplastic Agents, Immunological; Cell Adhesion Molecules; Drug Delivery Systems; Drug Therapy, Combination; Humans; Hyaluronoglucosaminidase; Immunoglobulins; Injections, Subcutaneous; Neoplasms; Recombinant Proteins
PubMed: 30744432
DOI: 10.1080/10717544.2018.1551442 -
Clinical Microbiology and Infection :... Jun 2018The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. (Review)
Review
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).
BACKGROUND
The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies.
AIMS
To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations.
SOURCES
Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family.
CONTENT
Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection.
IMPLICATIONS
Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Therapy; Clinical Trials as Topic; Communicable Disease Control; Communicable Diseases; Complement System Proteins; Dermatologic Agents; Humans; Immunocompromised Host; Immunoglobulins; Interleukin-17; Interleukins; Meningococcal Vaccines; Molecular Targeted Therapy
PubMed: 29447987
DOI: 10.1016/j.cmi.2018.02.002 -
Theranostics 2022In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis... (Review)
Review
In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their mechanisms and applications for cancer therapy. Further, based on the problems to be solved in the current clinical application of antibodies, and combined with the advanced drug delivery technologies, we discuss the roles of antibody-based drug delivery systems (DDSs) in cancer therapy, such as enhanced patient compliance and regulating the tumor microenvironment for combined therapy. By expounding the importance of DDSs and discussing the challenges and prospects of their implementation, we suggest that pharmaceutical enterprises and scientists develop appropriate antibody-based delivery platforms.
Topics: Antibodies; Drug Delivery Systems; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Tumor Microenvironment
PubMed: 35664074
DOI: 10.7150/thno.72594 -
Human Vaccines & Immunotherapeutics Apr 2022The use of antibodies in the treatment of lung diseases is of increasing interest especially as the search for COVID-19 therapies has unfolded. Historically, the use of... (Review)
Review
The use of antibodies in the treatment of lung diseases is of increasing interest especially as the search for COVID-19 therapies has unfolded. Historically, the use of antibody therapy was based on multiple targets including receptors involved in local hyper-reactivity in asthma, viruses and micro-organisms involved in a variety of pulmonary infectious disease. Generally, protein therapeutics pose challenges with respect to formulation and delivery to retain activity and assure therapy. The specificity of antibodies amplifies the need for attention to molecular integrity not only in formulation but also during aerosol delivery for pulmonary administration. Drug product development can be viewed from considerations of route of administration, dosage form, quality, and performance measures. Nebulizers and dry powder inhalers have been used to deliver protein therapeutics and each has its advantages that should be matched to the needs of the drug and the disease. This review offers insight into quality and performance barriers and the opportunities that arise from meeting them effectively.
Topics: Administration, Inhalation; Aerosols; Antibodies; Asthma; COVID-19; Drug Delivery Systems; Dry Powder Inhalers; Humans
PubMed: 34191682
DOI: 10.1080/21645515.2021.1940650 -
Molecules (Basel, Switzerland) Dec 2023Antibodies and their derivatives (scFv, Fabs, etc.) represent a unique class of biomolecules that combine selectivity with the ability to target drug delivery.... (Review)
Review
Antibodies and their derivatives (scFv, Fabs, etc.) represent a unique class of biomolecules that combine selectivity with the ability to target drug delivery. Currently, one of the most promising endeavors in this field is the development of molecular diagnostic tools and antibody-based therapeutic agents, including antibody-drug conjugates (ADCs). To meet this challenge, it is imperative to advance methods for modifying antibodies. A particularly promising strategy involves the introduction of carbonyl groups into the antibody that are amenable to further modification by biorthogonal reactions, namely aliphatic, aromatic, and α-oxo aldehydes, as well as aliphatic and aryl-alkyl ketones. In this review, we summarize the preparation methods and applications of site-specific antibody conjugates that are synthesized using this approach.
Topics: Antibodies; Immunoconjugates; Antigens; Drug Delivery Systems; Antineoplastic Agents
PubMed: 38067618
DOI: 10.3390/molecules28237890 -
Frontiers in Immunology 2018Immunotherapy is revolutionizing health care, with the majority of high impact "drugs" approved in the past decade falling into this category of therapy. Despite... (Review)
Review
Immunotherapy is revolutionizing health care, with the majority of high impact "drugs" approved in the past decade falling into this category of therapy. Despite considerable success, glycosylation-a key design parameter that ensures safety, optimizes biological response, and influences the pharmacokinetic properties of an immunotherapeutic-has slowed the development of this class of drugs in the past and remains challenging at present. This article describes how optimizing glycosylation through a variety of glycoengineering strategies provides enticing opportunities to not only avoid past pitfalls, but also to substantially improve immunotherapies including antibodies and recombinant proteins, and cell-based therapies. We cover design principles important for early stage pre-clinical development and also discuss how various glycoengineering strategies can augment the biomanufacturing process to ensure the overall effectiveness of immunotherapeutics.
Topics: Animals; Antibodies; Biological Products; Biomedical Engineering; Drug Design; Glycosylation; Humans; Immunotherapy; Quality Improvement; Recombinant Proteins
PubMed: 30450094
DOI: 10.3389/fimmu.2018.02485 -
International Journal of Molecular... May 2021Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic... (Review)
Review
Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.
Topics: Animals; Antibodies; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Apolipoproteins B; Atherosclerosis; Autoantibodies; Cardiovascular Diseases; Cholesterol, LDL; Cytokines; Humans; Immunization, Passive; Inflammation; Peptide Fragments; Proprotein Convertase 9; Stroke
PubMed: 34071276
DOI: 10.3390/ijms22115770 -
Pharmacology & Therapeutics Dec 2022Antibody therapy is effective for treating infectious diseases. Due to the coronavirus disease 2019 (COVID-19) pandemic and the rise of drug-resistant bacteria, rapid... (Review)
Review
Antibody therapy is effective for treating infectious diseases. Due to the coronavirus disease 2019 (COVID-19) pandemic and the rise of drug-resistant bacteria, rapid development of neutralizing monoclonal antibodies (mAbs) to treat infectious diseases is urgently needed. Using a therapeutic human mAb with the lowest immunogenicity is recommended, because chimera and humanized mAbs are occasionally immunogenic. In order to directly obtain naïve human mAbs, there are three methods: phage display, B cell receptor (BCR) cDNA sequencing of a single cell, and antibody-encoding gene and amino acid sequencing of immortalized cells using memory B cells, which are isolated from human peripheral blood mononuclear cells of healthy, vaccinated, infected, or recovered individuals. After screening against the antigen and performing neutralization assays, a human neutralizing mAb is constructed from the antibody-encoding DNA sequences of these memory B cells. This review describes examples of obtaining human neutralizing mAbs against various infectious diseases using these methods. However, a few of these mAbs have been approved for therapy. Therefore, antigen characterization and evaluation of neutralization activity in vitro and in vivo are indispensable for the development of therapeutic mAbs. These results will accelerate the development of antibody drug as therapeutic agents.
Topics: Humans; Antibodies, Monoclonal; Leukocytes, Mononuclear; Antibodies, Neutralizing; Communicable Diseases; COVID-19 Drug Treatment
PubMed: 35738431
DOI: 10.1016/j.pharmthera.2022.108233 -
Frontiers in Immunology 2023Significant progress has been made in the elucidation of human antibody repertoires. Furthermore, non-canonical functions of antibodies have been identified that reach... (Review)
Review
Significant progress has been made in the elucidation of human antibody repertoires. Furthermore, non-canonical functions of antibodies have been identified that reach beyond classical functions linked to protection from pathogens. Polyclonal immunoglobulin preparations such as IVIG and SCIG represent the IgG repertoire of the donor population and will likely remain the cornerstone of antibody replacement therapy in immunodeficiencies. However, novel evidence suggests that pooled IgA might promote orthobiotic microbial colonization in gut dysbiosis linked to mucosal IgA immunodeficiency. Plasma-derived polyclonal IgG and IgA exhibit immunoregulatory effects by a diversity of different mechanisms, which have inspired the development of novel drugs. Here we highlight recent insights into IgG and IgA repertoires and discuss potential implications for polyclonal immunoglobulin therapy and inspired drugs.
Topics: Humans; Immunoglobulins, Intravenous; Immunoglobulin G; Antibody Diversity; Immunologic Deficiency Syndromes; Immunization, Passive; Immunoglobulin A
PubMed: 37063852
DOI: 10.3389/fimmu.2023.1166821