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Emerging Microbes & Infections Dec 2023Since the onset of the coronavirus disease 2019 (COVID-19), numerous neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)... (Review)
Review
Since the onset of the coronavirus disease 2019 (COVID-19), numerous neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and authorized for emergency use to control the pandemic. Most COVID-19 therapeutic NAbs prevent the S1 subunit of the SARS-CoV-2 spike (S) protein from binding to the human host receptor. However, the emergence of SARS-CoV-2 immune escape variants, which possess frequent mutations on the S1 subunit, may render current NAbs ineffective. In contrast, the relatively conserved S2 subunit of the S protein can elicit NAbs with broader neutralizing potency against various SARS-CoV-2 variants. In this review, the binding specificity and functional features of SARS-CoV-2 NAbs targeting different domains of the S2 subunit are collectively discussed. The knowledge learned from the investigation of the S2-specific NAbs provides insights and potential strategies for developing antibody cocktail therapy and next-generation coronavirus vaccine.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Vaccines; Antibodies, Viral; Antibodies, Neutralizing; Spike Glycoprotein, Coronavirus
PubMed: 37254830
DOI: 10.1080/22221751.2023.2220582 -
Journal of Neurology Aug 2023New diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have recently been proposed, distinguishing this syndrome from other... (Review)
Review
New diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have recently been proposed, distinguishing this syndrome from other inflammatory diseases of the central nervous system. Seropositivity status for MOG-IgG autoantibodies is important for diagnosing MOGAD, but only in the context of robust clinical characterization and cautious interpretation of neuroimaging. Over the last several years, access to cell-based assay (CBA) techniques has improved diagnostic accuracy, yet the positive predictive value of serum MOG-IgG values varies with the prevalence of MOGAD in any given patient population. For this reason, possible alternative diagnoses need to be considered, and low MOG-IgG titers need to be carefully weighted. In this review, cardinal clinical features of MOGAD are discussed. Key challenges to the current understanding of MOGAD are also highlighted, including uncertainty regarding the specificity and pathogenicity of MOG autoantibodies, the need to identify immunopathologic targets for future therapies, the quest to validate biomarkers that facilitate diagnosis and detect disease activity, and the importance of deciphering which patients with MOGAD require long-term immunotherapy.
Topics: Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Central Nervous System; Immunotherapy; Immunoglobulin G; Aquaporin 4; Neuromyelitis Optica
PubMed: 37154894
DOI: 10.1007/s00415-023-11737-8 -
Frontiers in Pharmacology 2023Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid... (Review)
Review
Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tumor toxicity. Based on their beneficial mechanism of action, 15 ADCs have been approved to date by the market approval by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and/or other international governmental agencies for use in clinical oncology, and hundreds are undergoing evaluation in the preclinical and clinical phases. Here, our aim is to provide a comprehensive overview of the key features revolving around ADC therapeutic strategy including their structural and targeting properties, mechanism of action, the role of the tumor microenvironment and review the approved ADCs in clinical oncology, providing discussion regarding their toxicity profile, clinical manifestations and use in novel combination therapies. Finally, we briefly review ADCs in other pathological contexts and provide key information regarding ADC manufacturing and analytical characterization.
PubMed: 37790810
DOI: 10.3389/fphar.2023.1274088 -
Journal of Hematology & Oncology Jul 2023Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor... (Review)
Review
Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumomab) was approved by the FDA in 2014, but no other one hit the market until 2022. Now the field is gaining momentum, with three approvals in 2022 and 2023 (as of May): the anti-CD20 × anti-CD3 mosunetuzumab and epcoritamab and the anti-B cell maturation antigen (BCMA) × anti-CD3 teclistamab, and another three molecules in regulatory review. T cell engagers will likely revolutionize the treatment of hematological malignancies in the short term, as they are considerably more potent than conventional monoclonal antibodies recognizing the same tumor antigens. The field is thriving, with a plethora of different formats and targets, and around 100 bispecific T cell engagers more are already in clinical trials. Bispecific NK cell engagers are also in early-stage clinical studies and may offer similar efficacy with milder side effects. Trispecific antibodies (engaging either T cell or NK cell receptors) raise the game even further with a third binding moiety, which allows either the targeting of an additional tumor-associated antigen to increase specificity and avoid immune escape or the targeting of additional costimulatory receptors on the immune cell to improve its effector functions. Altogether, these engineered molecules may change the paradigm of treatment for relapsed or refractory hematological malignancies.
Topics: Humans; T-Lymphocytes; Antibodies, Bispecific; Immunotherapy; Hematologic Neoplasms; Killer Cells, Natural; Antigens, CD19; Antineoplastic Agents; Antigens, Neoplasm
PubMed: 37501154
DOI: 10.1186/s13045-023-01482-w -
ELife Nov 2023A strategy to identify high-quality commercially available antibodies for research reveals extensive use of non-specific antibodies and offers solutions for future...
A strategy to identify high-quality commercially available antibodies for research reveals extensive use of non-specific antibodies and offers solutions for future large-scale testing.
Topics: Antibodies; Antibody Specificity
PubMed: 37962204
DOI: 10.7554/eLife.93329 -
MAbs 2024Biparatopic antibodies (bpAbs) bind distinct, non-overlapping epitopes on an antigen. This unique binding mode enables new mechanisms of action beyond monospecific and... (Review)
Review
Biparatopic antibodies (bpAbs) bind distinct, non-overlapping epitopes on an antigen. This unique binding mode enables new mechanisms of action beyond monospecific and bispecific antibodies (bsAbs) that can make bpAbs effective therapeutics for various indications, including oncology and infectious diseases. Biparatopic binding can lead to superior affinity and specificity, promote antagonism, lock target conformation, and result in higher-order target clustering. Such antibody-target complexes can elicit strong agonism, increase immune effector function, or result in rapid target downregulation and lysosomal trafficking. These are not only attractive properties for therapeutic antibodies but are increasingly being explored for other modalities such as antibody-drug conjugates, T-cell engagers and chimeric antigen receptors. Recent advances in bpAb engineering have enabled the construction of ever more sophisticated formats that are starting to show promise in the clinic.
Topics: Immunoconjugates; Antibodies, Bispecific; Epitopes; Receptors, Chimeric Antigen
PubMed: 38439551
DOI: 10.1080/19420862.2024.2310890 -
Frontiers in Immunology 2023Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Global research efforts to improve TB control are hindered by insufficient understanding of... (Review)
Review
Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Global research efforts to improve TB control are hindered by insufficient understanding of the role that antibodies play in protective immunity and pathogenesis. This impacts knowledge of rational and optimal vaccine design, appropriate diagnostic biomarkers, and development of therapeutics. Traditional approaches for the prevention and diagnosis of TB may be less efficacious in high prevalence, remote, and resource-poor settings. An improved understanding of the immune response to the causative agent of TB, (), will be crucial for developing better vaccines, therapeutics, and diagnostics. While memory CD4+ T cells and cells and cytokine interferon gamma (IFN-g) have been the main identified correlates of protection in TB, mounting evidence suggests that other types of immunity may also have important roles. TB serology has identified antibodies and functional characteristics that may help diagnose infection and distinguish between different TB disease states. To date, no serological tests meet the World Health Organization (WHO) requirements for TB diagnosis, but multiplex assays show promise for improving the sensitivity and specificity of TB serodiagnosis. Monoclonal antibody (mAb) therapies and serum passive infusion studies in murine models of TB have also demonstrated some protective outcomes. However, animal models that better reflect the human immune response to are necessary to fully assess the clinical utility of antibody-based TB prophylactics and therapeutics. Candidate TB vaccines are not designed to elicit an -specific antibody response, but evidence suggests BCG and novel TB vaccines may induce protective antibodies. The potential of the humoral immune response in TB monitoring and control is being investigated and these studies provide important insight into the functional role of antibody-mediated immunity against TB. In this review, we describe the current state of development of antibody-based clinical tools for TB, with a focus on diagnostic, therapeutic, and vaccine-based applications.
Topics: Humans; Animals; Mice; Tuberculosis; Mycobacterium tuberculosis; Tuberculosis Vaccines; Cytokines; Interferon-gamma; Antibodies
PubMed: 38162666
DOI: 10.3389/fimmu.2023.1278947 -
Frontiers in Oncology 2023Although the six-transmembrane epithelial antigen of prostate 1 (STEAP1) was first identified in advanced prostate cancer, its overexpression is recognized in multiple... (Review)
Review
Although the six-transmembrane epithelial antigen of prostate 1 (STEAP1) was first identified in advanced prostate cancer, its overexpression is recognized in multiple types of cancer and associated with a poor prognosis. STEAP1 is now drawing attention as a promising therapeutic target because of its tumor specificity and membrane-bound localization. The clinical efficacy of an antibody-drug conjugate targeting STEAP1 in metastatic, castration-resistant, prostate cancer was demonstrated in a phase 1 trial. Furthermore, growing evidence suggests that STEAP1 is an attractive target for immunotherapies such as chimeric antigen receptor-T cell therapy. In this review, we summarize the oncogenic functions of STEAP1 by cancer type. This review also provides new insights into the development of new anticancer strategies targeting STEAP1.
PubMed: 37909017
DOI: 10.3389/fonc.2023.1285661