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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 -
Nephrology, Dialysis, Transplantation :... Feb 2024Membranous nephropathy (MN) is characterized by deposition of immune complexes leading to thickening of glomerular basement membranes. Over time, the understanding of MN... (Review)
Review
Membranous nephropathy (MN) is characterized by deposition of immune complexes leading to thickening of glomerular basement membranes. Over time, the understanding of MN has evolved, with the identification of specific autoantibodies against novel podocyte antigens and the unraveling of intricate pathogenic pathways. Although the anti-CD20 monoclonal antibody rituximab is favored as part of the initial therapy in MN, a subgroup of MN patients may be resistant to rituximab necessitating the use of alternative agents such as cytotoxic therapies. In addition, newer agents such as novel anti-CD20 monoclonal antibodies, therapies targeting the CD38-positive plasma cells and anti-complement therapy are being studied in patients who are resistant to traditional treatment strategies. This manuscript furnishes a review of the novel developments in the pathophysiology of MN including the identification of target antigens and current treatment standards for MN, concentrating on evidenced-based interventions designed to attain remission and to prevent disease progression.
Topics: Humans; Glomerulonephritis, Membranous; Rituximab; Antibodies, Monoclonal; Autoantibodies; Antigen-Antibody Complex; Receptors, Phospholipase A2
PubMed: 37934599
DOI: 10.1093/ndt/gfad225 -
Nature Reviews. Drug Discovery Aug 2019The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats,... (Review)
Review
The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from relatively small proteins, merely consisting of two linked antigen-binding fragments, to large immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb feature is their potential for novel functionalities - that is, activities that do not exist in mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the physical linkage of the two binding specificities creates a dependency that can be temporal, with binding events occurring sequentially, or spatial, with binding events occurring simultaneously, such as in linking an effector to a target cell. To date, more than 20 different commercialized technology platforms are available for bsAb creation and development, 2 bsAbs are marketed and over 85 are in clinical development. Here, we review the current bsAb landscape from a mechanistic perspective, including a comprehensive overview of the pipeline.
Topics: Animals; Antibodies, Bispecific; Binding Sites, Antibody; Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; Humans; Molecular Targeted Therapy; Neoplasms
PubMed: 31175342
DOI: 10.1038/s41573-019-0028-1 -
European Journal of Haematology Nov 2022This paper reviews current and emerging therapies for multiple myeloma (MM). (Review)
Review
OBJECTIVES
This paper reviews current and emerging therapies for multiple myeloma (MM).
METHODS
Narrative review.
RESULTS
MM is a complex, heterogenous condition, and in recent years there has been an expansion in the number and range of treatments. Several new treatment approaches, including enhanced monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen-T-cell therapy are under development.
CONCLUSIONS
The emergence of new treatments that aim to tackle MM-associated immune dysfunction has led to improvements in overall survival.
Topics: Antibodies, Monoclonal; Humans; Immunoconjugates; Immunotherapy; Immunotherapy, Adoptive; Multiple Myeloma
PubMed: 35880395
DOI: 10.1111/ejh.13840 -
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 -
Drugs Jul 2022Mosunetuzumab (Lunsumio), an anti-CD20/CD3 T-cell engaging bispecific antibody, is being developed by Roche for the treatment of relapsed or refractory follicular... (Review)
Review
Mosunetuzumab (Lunsumio), an anti-CD20/CD3 T-cell engaging bispecific antibody, is being developed by Roche for the treatment of relapsed or refractory follicular lymphoma. Mosunetuzumab was recently conditionally approved in the EU for the treatment of relapsed or refractory follicular lymphoma in adults who have received at least two prior systemic therapies. This article summarizes the milestones in the development of mosunetuzumab leading to this first approval for relapsed or refractory follicular lymphoma.
Topics: Adult; Antibodies, Bispecific; Antigens, CD20; Antineoplastic Agents; Humans; Immunotherapy; Lymphoma, Follicular
PubMed: 35947358
DOI: 10.1007/s40265-022-01749-5 -
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