-
Immunity Jun 2022Neutralizing antibodies can block infection, clear pathogens, and are essential to provide long-term immunity. Since the onset of the pandemic, SARS-CoV-2 neutralizing... (Review)
Review
Neutralizing antibodies can block infection, clear pathogens, and are essential to provide long-term immunity. Since the onset of the pandemic, SARS-CoV-2 neutralizing antibodies have been comprehensively investigated and critical information on their development, function, and potential use to prevent and treat COVID-19 have been revealed. With the emergence of SARS-CoV-2 immune escape variants, humoral immunity is being challenged, and a detailed understanding of neutralizing antibodies is essential to guide vaccine design strategies as well as antibody-mediated therapies. In this review, we summarize some of the key findings on SARS-CoV-2 neutralizing antibodies, with a focus on their clinical application.
Topics: Antibodies, Neutralizing; Antibodies, Viral; COVID-19; Humans; Neutralization Tests; SARS-CoV-2; Vaccination
PubMed: 35623355
DOI: 10.1016/j.immuni.2022.05.005 -
International Journal of Molecular... Feb 2021Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant... (Review)
Review
Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment options in oncology, and an in-depth discussion of the therapeutics in the preclinical stage for the treatment of breast cancer, lung cancer, and multiple myeloma.
Topics: Antibodies, Monoclonal; Cell- and Tissue-Based Therapy; Genetic Therapy; Humans; Immunoconjugates; Immunotherapy; Medical Oncology; Molecular Targeted Therapy; Neoplasms; Small Molecule Libraries
PubMed: 33670524
DOI: 10.3390/ijms22042008 -
Journal of Pharmaceutical Sciences May 2019Protein therapeutics have drastically changed the landscape of treatment for many diseases by providing a regimen that is highly specific and lacks many off-target... (Review)
Review
Protein therapeutics have drastically changed the landscape of treatment for many diseases by providing a regimen that is highly specific and lacks many off-target toxicities. The clinical utility of many therapeutic proteins has been undermined by the potential development of unwanted immune responses against the protein, limiting their efficacy and negatively impacting its safety profile. This review attempts to provide an overview of immunogenicity of therapeutic proteins, including immune mechanisms and factors influencing immunogenicity, impact of immunogenicity, preclinical screening methods, and strategies to mitigate immunogenicity.
Topics: Animals; Antibodies; Antibody Formation; Humans; Proteins
PubMed: 30599169
DOI: 10.1016/j.xphs.2018.12.014 -
Nature Reviews. Cancer Jun 2015For 20 years, monoclonal antibodies (mAbs) have been a standard component of cancer therapy, but there is still much room for improvement. Efforts continue to build... (Review)
Review
For 20 years, monoclonal antibodies (mAbs) have been a standard component of cancer therapy, but there is still much room for improvement. Efforts continue to build better cancer therapeutics based on mAbs. Anticancer mAbs function through various mechanisms, including directly targeting the malignant cells, modifying the host response, delivering cytotoxic moieties and retargeting cellular immunity towards the malignant cells. Characteristics of mAbs that affect their efficacy include antigen specificity, overall structure, affinity for the target antigen and how a mAb component is incorporated into a construct that can trigger target cell death. This Review discusses the various approaches to using mAb-based therapeutics to treat cancer and the strategies used to take advantage of the unique potential of each approach, and provides examples of current mAb-based treatments.
Topics: Animals; Antibodies, Bispecific; Antibodies, Monoclonal; Antineoplastic Agents; Humans; Immunoconjugates; Molecular Targeted Therapy; Neoplasms; Neovascularization, Pathologic; Signal Transduction; T-Lymphocytes
PubMed: 25998715
DOI: 10.1038/nrc3930 -
The Lancet. Infectious Diseases Nov 2022Monoclonal antibodies (mAbs) targeting the spike protein of SARS-CoV-2 have been widely used in the ongoing COVID-19 pandemic. In this paper, we review the properties of... (Review)
Review
Monoclonal antibodies (mAbs) targeting the spike protein of SARS-CoV-2 have been widely used in the ongoing COVID-19 pandemic. In this paper, we review the properties of mAbs and their effect as therapeutics in the pandemic, including structural classification, outcomes in clinical trials that led to the authorisation of mAbs, and baseline and treatment-emergent immune escape. We show how the omicron (B.1.1.529) variant of concern has reset treatment strategies so far, discuss future developments that could lead to improved outcomes, and report the intrinsic limitations of using mAbs as therapeutic agents.
Topics: Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Pandemics; COVID-19; Antibodies, Monoclonal; Antibodies, Viral; Antibodies, Neutralizing
PubMed: 35803289
DOI: 10.1016/S1473-3099(22)00311-5 -
Frontiers in Immunology 2022Chronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other... (Review)
Review
INTRODUCTION
Chronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.
MATERIALS AND METHODS
We systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.
RESULTS
Most studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.
CONCLUSION
TCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.
Topics: Antibodies, Monoclonal, Humanized; Female; Graft Rejection; Graft Survival; HLA Antigens; Humans; Inflammation; Isoantibodies; Kidney Transplantation; Male
PubMed: 35493469
DOI: 10.3389/fimmu.2022.839380 -
Biochimie Oct 2020An antibody's stability greatly influences its performance (i.e. its specificity and affinity). Thus, stability is a major issue for researchers and manufacturers,... (Review)
Review
An antibody's stability greatly influences its performance (i.e. its specificity and affinity). Thus, stability is a major issue for researchers and manufacturers, especially with the increasing use of antibodies in therapeutics, diagnostics and rapid analytical platforms. Here we review antibody stability under five headings: (i) measurement techniques; (ii) stability issues in expression and production (expression, proteolysis, aggregation); (iii) effects of antibody format and engineering on stability and (iv) formulation, drying and storage conditions. We consider more than 100 sources, including patents, and conclude with (v) recommendations to promote antibody stability.
Topics: Animals; Antibodies; Cold Temperature; Drug Compounding; Drug Storage; Humans; Protein Engineering; Protein Stability
PubMed: 32891698
DOI: 10.1016/j.biochi.2020.08.019 -
Cancer Research Sep 2021Monoclonal antibodies (mAb) are a major component of cancer therapy. In this review, we summarize the different therapeutic mAbs that have been successfully developed... (Review)
Review
Monoclonal antibodies (mAb) are a major component of cancer therapy. In this review, we summarize the different therapeutic mAbs that have been successfully developed against various tumor-expressed antigens and examine our current understanding of their different mechanisms of antitumor action. These mechanisms of action (MOA) largely center on the stimulation of different innate immune effector processes, which appear to be principally responsible for the efficacy of most unconjugated mAb therapies against cancer. This is evident in studies of mAbs targeting antigens for hematologic cancers, with emerging data also demonstrating the critical nature of innate immune-mediated mechanisms in the efficacy of anti-HER2 mAbs against solid HER2 cancers. Although HER2-targeted mAbs were originally described as inhibitors of HER2-mediated signaling, multiple studies have since demonstrated these mAbs function largely through their engagement with Fc receptors to activate innate immune effector functions as well as complement activity. Next-generation mAbs are capitalizing on these MOAs through improvements to enhance Fc-activity, although regulation of these mechanisms may vary in different tumor microenvironments. In addition, novel antibody-drug conjugates have emerged as an important means to activate different MOAs. Although many unknowns remain, an improved understanding of these immunologic MOAs will be essential for the future of mAb therapy and cancer immunotherapy.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Susceptibility; Hematologic Neoplasms; Humans; Immunoconjugates; Molecular Targeted Therapy; Neoplasms; Prognosis; Treatment Outcome
PubMed: 34145037
DOI: 10.1158/0008-5472.CAN-21-1109 -
Current Opinion in Organ Transplantation Oct 2022Antibody-mediated rejection (AMR) has emerged as the leading cause of late graft loss in kidney transplant recipients. Donor-specific antibodies are an independent risk... (Review)
Review
PURPOSE OF REVIEW
Antibody-mediated rejection (AMR) has emerged as the leading cause of late graft loss in kidney transplant recipients. Donor-specific antibodies are an independent risk factor for AMR and graft loss. However, not all donor-specific antibodies are pathogenic. AMR treatment is heterogeneous due to the lack of robust trials to support clinical decisions. This review provides an overview and comments on practical but relevant dilemmas physicians experience in managing kidney transplant recipients with AMR.
RECENT FINDINGS
Active AMR with donor-specific antibodies may be treated with plasmapheresis, intravenous immunoglobulin and corticosteroids with additional therapies considered on a case-by-case basis. On the contrary, no treatment has been shown to be effective against chronic active AMR. Various biomarkers and prediction models to assess the individual risk of graft failure and response to rejection treatment show promise.
SUMMARY
The ability to personalize management for a given kidney transplant recipient and identify treatments that will improve their long-term outcome remains a critical unmet need. Earlier identification of AMR with noninvasive biomarkers and prediction models to assess the individual risk of graft failure should be considered. Enrolling patients with AMR in clinical trials to assess novel therapeutic agents is highly encouraged.
Topics: Antibodies; Biomarkers; Graft Rejection; Graft Survival; Humans; Isoantibodies; Kidney Transplantation; Plasmapheresis
PubMed: 35950887
DOI: 10.1097/MOT.0000000000001011 -
Current Gastroenterology Reports Jun 2020Biologics for the treatment of inflammatory bowel disease (IBD) have been transformative to the therapeutic goals in the pediatric population. We review the biologics... (Review)
Review
PURPOSE OF REVIEW
Biologics for the treatment of inflammatory bowel disease (IBD) have been transformative to the therapeutic goals in the pediatric population. We review the biologics used to treat IBD, highlighting the importance of patient selection, dosing considerations, and therapeutic drug monitoring in children.
RECENT FINDINGS
Infliximab is well-established as a safe and efficacious therapy for Crohn's disease and ulcerative colitis. Both dose escalation strategies and therapeutic drug monitoring increase the likelihood of response to anti-TNFα therapies. Early real-world experience of vedolizumab and ustekinumab in pediatric IBD shows promising results, including clinical response rates comparable to what is seen in adults, but there are limited data using them as first-line therapies. Biologic therapies have improved outcomes in pediatric IBD, including achieving mucosal healing as well as improved growth and pubertal development. Therapeutic drug monitoring improves likelihood of response to anti-TNFα therapies, but further studies for vedolizumab and ustekinumab are necessary.
Topics: Antibodies, Monoclonal, Humanized; Biological Products; Biological Therapy; Child; Dose-Response Relationship, Drug; Drug Monitoring; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Infliximab; Patient Selection; Ustekinumab
PubMed: 32542562
DOI: 10.1007/s11894-020-00773-3