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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 -
Medecine Sciences : M/S Dec 2019Cytokines and biological toxins represent two potent classes of biomolecules that have long been explored for their potential as therapeutics. Considerable side effects... (Review)
Review
Cytokines and biological toxins represent two potent classes of biomolecules that have long been explored for their potential as therapeutics. Considerable side effects and poor pharmacokinetics frequently observed with both have limited their broad application. Recombinant protein engineering has allowed the construction of immunocytokines and immunotoxins that seek to exploit the advantageous properties of immunoglobulins to address these issues. Whole antibodies, antibody fragments, constant domains and derivatives have been fused genetically to a range of cytokines and toxins. This review considers the strategies that have been employed and the problems sought to be resolved in the clinical evaluation of this class of biotherapeutic.
Topics: Animals; Antibodies; Cytokines; Drug Evaluation, Preclinical; Humans; Immunotoxins; Protein Engineering; Recombinant Fusion Proteins
PubMed: 31903917
DOI: 10.1051/medsci/2019205 -
Cell Reports May 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody. LY-CoV1404 potently neutralizes authentic SARS-CoV-2, B.1.1.7, B.1.351, and B.1.617.2. In pseudovirus neutralization studies, LY-CoV1404 potently neutralizes variants, including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved, except for N439 and N501. The binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The broad and potent neutralization activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Epitopes; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35568025
DOI: 10.1016/j.celrep.2022.110812 -
Handbook of Experimental Pharmacology 2022Prevention of allograft rejection is one of the crucial goals in solid organ transplantation to ensure durability of the graft and is chiefly mediated by cellular and...
Prevention of allograft rejection is one of the crucial goals in solid organ transplantation to ensure durability of the graft and is chiefly mediated by cellular and humoral pathways targeting cell surface alloantigens. The risk of rejection is highest in the first post-transplant year and wanes with time albeit the risk always exists and varies with the type of organ transplanted. Induction therapies refer to the use of high-intensity immunosuppression in the immediate post-operative period to mitigate the highest risk of rejection. This term encompasses chiefly the use of antibody therapies directed against one of the key pathways in T-cell activation or abrogating effects of circulating alloantibodies. These antibodies carry more potent immunomodulatory effect than maintenance immunosuppressive therapy alone and many of them lead to durable immune cell depletion. A variety of monoclonal and polyclonal antibodies have been utilized for use not only for induction therapy, but also for treatment of allograft rejection when it occurs and as components of desensitization therapy before and after transplantation to modulate circulating alloantibodies.
Topics: Antibodies, Monoclonal; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Induction Chemotherapy; Isoantibodies
PubMed: 35474024
DOI: 10.1007/164_2021_570 -
Frontiers of Medicine Dec 2023The epidemic of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern (VOCs) has been ongoing for... (Review)
Review
The epidemic of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern (VOCs) has been ongoing for over 3 years. Antibody therapies encompassing convalescent plasma, hyperimmunoglobulin, and neutralizing monoclonal antibodies (mAbs) applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment. In this review, the development path, action mechanism, clinical research results, challenges, and safety profile associated with the use of COVID-19 convalescent plasma, hyperimmunoglobulin, and mAbs were summarized. In addition, the prospects of applying antibody therapy against VOCs was assessed, offering insights into the coping strategies for facing new infectious disease outbreaks.
Topics: Humans; Antibodies, Viral; Communicable Diseases, Emerging; COVID-19 Drug Treatment; COVID-19; SARS-CoV-2; Antibodies, Neutralizing
PubMed: 38040914
DOI: 10.1007/s11684-023-1021-y -
American Journal of Clinical Dermatology Dec 2020Pemphigus vulgaris (PV) is a severe chronic autoimmune blistering disease that affects the skin and mucous membranes. It is characterized by suprabasal acantholysis due... (Review)
Review
Pemphigus vulgaris (PV) is a severe chronic autoimmune blistering disease that affects the skin and mucous membranes. It is characterized by suprabasal acantholysis due to disruption of desmosomal connections between keratinocytes. Autoantibodies against desmosomal cadherins, desmoglein 3 and 1, have been shown to induce disease. Certain human leukocyte antigen (HLA) types and non-HLA foci confer genetic susceptibility. Until the discovery of corticosteroids in the 1950s, PV was 75% fatal. Since then, multiple PV treatments, such as systemic corticosteroids and adjunctive therapy with immunosuppressive medications (mycophenolate mofetil, azathioprine, cyclophosphamide, cyclosporine, methotrexate, gold, and others) have been introduced; however, none have led to long-term remissions and many have undesired adverse effects. Our growing understanding of the pathophysiologic mechanisms in PV is leading to development of new targeted therapies, such as intravenous immunoglobulin, anti-CD20 monoclonal antibodies, inhibitors of Bruton tyrosine kinase and neonatal Fc receptors, and adoptive cellular transfer, that may result in lasting control of this life-threatening disease.
Topics: Agammaglobulinaemia Tyrosine Kinase; Antibodies, Monoclonal; Antigens, CD20; Autoantibodies; Combined Modality Therapy; Drug Therapy, Combination; Genetic Predisposition to Disease; HLA Antigens; Histocompatibility Antigens Class I; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy, Adoptive; Molecular Targeted Therapy; Pemphigus; Plasmapheresis; Receptors, Fc; Remission Induction; Signal Transduction; Treatment Outcome
PubMed: 32860200
DOI: 10.1007/s40257-020-00544-w -
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 -
Pharmacology & Therapeutics Sep 2022Bispecific antibodies (BsAb) are a new generation of antibody-based therapy, conveying artificial specificity to polyclonal T cells or radiohaptens. These drugs have... (Review)
Review
Bispecific antibodies (BsAb) are a new generation of antibody-based therapy, conveying artificial specificity to polyclonal T cells or radiohaptens. These drugs have been successfully implemented to cure hematologic malignancies and are under clinical investigation for solid tumors including HRNB. BsAbs designed to engage T cells or increase the therapeutic index of radiotherapy hold the potential to significantly improve the long-term survival of HRNB patients by shrinking bulky tumors and more effectively eliminating micrometastases and preventing relapse. BsAbs can also be used to arm T cells, yielding a product analogous to CAR T cells, possibly with an improved safety profile. A thoughtful and realistic integration of these therapies into the standard of care should benefit more patients worldwide. Here we describe the history of development of BsAbs for HRNB, which dates back almost three decades. We discuss the merits and pitfalls of all relevant BsAbs, including T cell-engagers and agents used for radioimmunotherapy, highlighting the importance of structural design and interdomain spacing for anti-tumor efficacy.
Topics: Antibodies, Bispecific; Humans; Immunotherapy; Neoplasm Recurrence, Local; Neuroblastoma; Radioimmunotherapy
PubMed: 35830901
DOI: 10.1016/j.pharmthera.2022.108241 -
Expert Opinion on Biological Therapy Feb 2020: The toxicity of potent new biological therapies for cancer has limited their utility. By improving tumor specificity, antibody prodrugs can widen or even create a... (Review)
Review
: The toxicity of potent new biological therapies for cancer has limited their utility. By improving tumor specificity, antibody prodrugs can widen or even create a therapeutic window for anticancer agents that are difficult or impossible to use otherwise because of poor tolerability.: This review will describe the current status of the field of antibody prodrugs, focusing on Probody therapeutics, including the principles behind their design, application to a variety of different antibody-based therapies, preclinical examples of their activity and safety, and early results of Phase 1 trials.: Proof of concept for the antibody prodrug approach, which is defined as demonstration of potent antitumor activity with improved safety, has been extensively established preclinically as well as preliminarily in early clinical trials in human patients. However, experience with antibody prodrugs is limited, and important challenges remain. Principal among them are how to design the molecules to provide the most effective protection from toxicities while preserving efficacy, how to optimize clinical pharmacology, and how to determine which among the many possible clinical applications is the best use of this promising technology.
Topics: Animals; Antibodies; Antineoplastic Agents, Immunological; Drug-Related Side Effects and Adverse Reactions; Humans; Immunotherapy; Neoplasms; Prodrugs
PubMed: 31779489
DOI: 10.1080/14712598.2020.1699053 -
The Journal of Infectious Diseases Nov 2023Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as...
Filoviruses, including ebolaviruses and marburgviruses, can cause severe and often fatal disease in humans. Over the past several years, antibody therapy has emerged as a promising strategy for the treatment of filovirus disease. Here, we describe 2 distinct cross-reactive monoclonal antibodies (mAbs) isolated from mice immunized with recombinant vesicular stomatitis virus-based filovirus vaccines. Both mAbs recognized the glycoproteins of multiple different ebolaviruses and exhibited broad but differential in vitro neutralization activities against these viruses. By themselves, each mAb provided partial to full protection against Ebola virus in mice, and in combination, the mAbs provided 100% protection against Sudan virus challenge in guinea pigs. This study identified novel mAbs that were elicited through immunization and able to provide protection from ebolavirus infection, thus enriching the pool of candidate therapeutics for treating Ebola disease.
Topics: Humans; Animals; Guinea Pigs; Mice; Hemorrhagic Fever, Ebola; Ebolavirus; Antibodies, Monoclonal; Combined Antibody Therapeutics; Antibodies, Neutralizing; Antibodies, Viral
PubMed: 37288609
DOI: 10.1093/infdis/jiad205