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Annual Review of Medicine Jan 2024Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable... (Review)
Review
Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable suite of new therapies developed over the last 25 years has enabled durable disease control in most patients. This article briefly introduces the clinical features of multiple myeloma and aspects of multiple myeloma biology that modern therapies exploit. Key current and emerging treatment modalities are then reviewed, including cereblon-modulating agents, proteasome inhibitors, monoclonal antibodies, other molecularly targeted therapies (selinexor, venetoclax), chimeric antigen receptor T cells, T cell-engaging bispecific antibodies, and antibody-drug conjugates. For each modality, mechanism of action and clinical considerations are discussed. These therapies are combined and sequenced in modern treatment pathways, discussed at the conclusion of the article, which have led to substantial improvements in outcomes for multiple myeloma patients in recent years.
Topics: Humans; Multiple Myeloma; Immunotherapy; Proteasome Inhibitors; Antibodies, Monoclonal; Biological Therapy
PubMed: 37729027
DOI: 10.1146/annurev-med-050522-033815 -
Swiss Medical Weekly May 2022Severe asthma is associated with increased morbidity, mortality, healthcare costs and impaired quality of life. Asthma is no longer considered as a single entity but as... (Review)
Review
Severe asthma is associated with increased morbidity, mortality, healthcare costs and impaired quality of life. Asthma is no longer considered as a single entity but as a heterogeneous disease with different clinical presentations (phenotypes) and variable underlying mechanistic biological pathways (endotypes). Two different endotypes are based on the inflammatory Type 2 T-helper response: T2-high and T2-low. The understanding of these endotypes has revolutionised the management of severe asthma. Recent guidelines from the 2019 European Respiratory Society/American Thoracic Society (ERS/ATS) and Global Initiative for Asthma (GINA) 2021 specifically address the diagnosis and the management of severe asthma in adults, but less evidence exists for the paediatric population. Presently, five biologics for the treatment of severe asthma are approved, i.e., omalizumab (anti-IgE antibody), mepolizumab and reslizumab (anti-IL-5 antibody), benralizumab (anti-IL-5 receptor antibody) and dupilumab (anti-IL-4 receptor alpha antibody). This article reviews the pathological mechanisms of severe asthma, clinical biomarkers related to the T2-high endotype, and their use for the prediction of the severity of the disease and response to biological therapy. Furthermore, future developments of biologics for severe asthma are presented.
Topics: Adolescent; Anti-Asthmatic Agents; Asthma; Biological Products; Biological Therapy; Humans; Quality of Life
PubMed: 35748315
DOI: 10.4414/smw.2022.w30176 -
International Journal of Molecular... Nov 2017Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised... (Review)
Review
Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised small molecule drugs, targeting the immune system in a non-specific manner. The first biologics targeted T-cell activation and migration and served as an alternative to small molecules. However, significant improvement in outcome was first accomplished with the introduction of tumor necrosis factor-α inhibitors that were already approved for other inflammatory disorders, including rheumatic diseases. Along with the progress in understanding psoriasis pathogenesis, highly targeted and effective therapies have since developed with the perspective not only to improve but to clear psoriasis. These accomplishments enable future achievement of advanced goals to individualize treatment best suited for each patient. Mechanistic studies with patients treated with the new highly targeted biologics may guide us towards these goals. This review offers an overview of biologics developed for psoriasis and illustrate a historical progress in the treatment of this common chronic inflammatory skin condition.
Topics: Animals; Biological Products; Biological Therapy; Biosimilar Pharmaceuticals; Humans; Psoriasis
PubMed: 29104241
DOI: 10.3390/ijms18112297 -
Science (New York, N.Y.) Jun 2016The study of RNA has continually emphasized the structural and functional versatility of RNA molecules. This versatility has inspired translational and clinical... (Review)
Review
The study of RNA has continually emphasized the structural and functional versatility of RNA molecules. This versatility has inspired translational and clinical researchers to explore the utility of RNA-based therapeutic agents for a wide variety of medical applications. Several RNA therapeutics, with diverse modes of action, are being evaluated in large late-stage clinical trials, and many more are in early clinical development. Hundreds of patients are enrolled in large trials testing messenger RNAs to combat cancer, small interfering RNAs to treat renal and hepatic disorders, and aptamers to combat ocular and cardiovascular disease. Results from these studies are generating considerable interest among the biomedical community and the public and will be important for the future development of this emerging class of therapeutic agents.
Topics: Animals; Biological Therapy; Cancer Vaccines; Cellular Reprogramming Techniques; Humans; Immunotherapy; Protein Biosynthesis; Proteins; RNA, Long Noncoding; RNA, Messenger; RNA, Small Interfering
PubMed: 27313039
DOI: 10.1126/science.aad8709 -
Osteoarthritis and Cartilage Feb 2016The intervertebral disc (IVD) is composed of the external annulus fibrosus (AF) and the inner gel-like center, the nucleus pulposus (NP). The elastic NP can function to... (Review)
Review
OBJECTIVE
The intervertebral disc (IVD) is composed of the external annulus fibrosus (AF) and the inner gel-like center, the nucleus pulposus (NP). The elastic NP can function to relieve stress and maintain IVD function by distributing hydraulic pressure evenly to annulus and endplate. Degeneration of the NP, which leads to increased death of NP cells, the loss of proteoglycan (PG), and aberrant gene expression, may result in an overall alteration of the biomechanics of the spinal column and cause low back pain. Recent advances in biological therapy strategies that target therapy at the regeneration of degenerated and damaged NP have been investigated in in vitro and in vivo studies and demonstrated promising outcomes. In this article, we review recent studies of biological approaches for NP regeneration.
METHOD
The articles regarding NP regeneration using biomaterials, stem cells, and gene vectors were identified in PubMed databases.
RESULTS
Stem cell-mediated cell therapy demonstrates the potential to restore the function and structure of the NP. The viral or non-viral vectors encoding functional genes may generate a therapeutic effect when they are introduced into grafted cells or native cells in the NP. Biomaterial scaffolds generate an initial permissive environment for cell growth and allow the remodeling of scaffolds in the regeneration process. Biomaterial scaffolds provide structural support for NP regeneration and serve as a carrier for stem cell and gene vector delivery.
CONCLUSION
Though recent studies advance the body of knowledge needed to treat degenerated discs, many challenges need to be overcome before the application of these approaches can be successful clinically.
Topics: Genetic Therapy; Humans; In Vitro Techniques; Intervertebral Disc; Intervertebral Disc Degeneration; Regeneration; Stem Cell Transplantation; Tissue Scaffolds
PubMed: 26342641
DOI: 10.1016/j.joca.2015.08.014 -
Polish Archives of Internal Medicine Aug 2022
Topics: Biological Therapy; Chronic Disease; Humans; Inflammatory Bowel Diseases; Treatment Outcome
PubMed: 35993835
DOI: 10.20452/pamw.16309 -
Frontiers in Immunology 2018The use of extracellular vesicles (EVs) as a potential therapy is currently explored for different disease areas. When it comes to the treatment of joint diseases this... (Review)
Review
The use of extracellular vesicles (EVs) as a potential therapy is currently explored for different disease areas. When it comes to the treatment of joint diseases this approach is still in its infancy. As in joint diseases both inflammation and the associated articular tissue destruction are important factors, both the immune-suppressive and the regenerative properties of EVs are potentially advantageous characteristics for future therapy. There is, however, only limited knowledge on the basic features, such as numerical profile and function, of EVs in joint articular tissues in general and their linking medium, the synovial fluid, in particular. Further insight is urgently needed in order to appreciate the full potential of EVs and to exploit these in EV-mediated therapies. Physiologic joint homeostasis is a prerequisite for proper functioning of joints and we postulate that EVs play a key role in the regulation of joint homeostasis and hence can have an important function in re-establishing disturbed joint homeostasis, and, in parallel, in the regeneration of articular tissues. In this mini-review EVs in the joint are explained from a historical perspective in both health and disease, including the potential niche for EVs in articular tissue regeneration. Furthermore, the translational potential of equine models for human joint biology is discussed. Finally, the use of MSC-derived EVs that is recently gaining ground is highlighted and recommendations are given for further EV research in this field.
Topics: Animals; Biological Therapy; Disease Models, Animal; Extracellular Vesicles; Homeostasis; Horses; Humans; Joint Diseases; Joints; Mesenchymal Stem Cells; Regeneration; Stem Cell Niche
PubMed: 30483255
DOI: 10.3389/fimmu.2018.02575 -
Reumatologia Clinica 2019
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Biological Therapy; Humans
PubMed: 30709786
DOI: 10.1016/j.reuma.2018.12.006 -
Journal For Immunotherapy of Cancer Aug 2018In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting ('Microbial Based Cancer Therapy') at the US National... (Review)
Review
In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting ('Microbial Based Cancer Therapy') at the US National Cancer Institute in the summer of 2017. Here, we define 'Microbial Therapy' to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care.
Topics: Animals; Bacteria; Biological Therapy; Cancer Vaccines; Clinical Studies as Topic; Combined Modality Therapy; Drug Evaluation, Preclinical; Genetic Engineering; Genetic Vectors; Humans; Neoplasms; Oncolytic Virotherapy; Treatment Outcome; Viruses
PubMed: 30081947
DOI: 10.1186/s40425-018-0381-3 -
Nature Reviews. Microbiology May 2020Antibacterial resistance is a great concern and requires global action. A critical question is whether enough new antibacterial drugs are being discovered and developed.... (Review)
Review
Antibacterial resistance is a great concern and requires global action. A critical question is whether enough new antibacterial drugs are being discovered and developed. A review of the clinical antibacterial drug pipeline was recently published, but comprehensive information about the global preclinical pipeline is unavailable. This Review focuses on discovery and preclinical development projects and has found, as of 1 May 2019, 407 antibacterial projects from 314 institutions. The focus is on Gram-negative pathogens, particularly bacteria on the WHO priority bacteria list. The preclinical pipeline is characterized by high levels of diversity and interesting scientific concepts, with 135 projects on direct-acting small molecules that represent new classes, new targets or new mechanisms of action. There is also a strong trend towards non-traditional approaches, including diverse antivirulence approaches, microbiome-modifying strategies, and engineered phages and probiotics. The high number of pathogen-specific and adjunctive approaches is unprecedented in antibiotic history. Translational hurdles are not adequately addressed yet, especially development pathways to show clinical impact of non-traditional approaches. The innovative potential of the preclinical pipeline compared with the clinical pipeline is encouraging but fragile. Much more work, focus and funding are needed for the novel approaches to result in effective antibacterial therapies to sustainably combat antibacterial resistance.
Topics: Anti-Bacterial Agents; Bacterial Infections; Biological Therapy; Drug Discovery; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Treatment Outcome
PubMed: 31745331
DOI: 10.1038/s41579-019-0288-0