Showing papers in "Expert Opinion on Biological Therapy in 2019"
TL;DR: This review provides an overview of wound healing and current methods for the management of chronic wounds, as well as the current state and considerations for optimizing stem cell therapy, which have been shown to accelerate wound healing by modulating the immune response and promoting angiogenesis.
Abstract: Introduction: Aberrant wound healing is a significant healthcare problem, posing a substantial burden on patients, their families, and the healthcare system. Existing treatment options remain only ...
109 citations
TL;DR: A major unmet need is the identification of biomarkers that can predict response to therapy and facilitate a personalized therapeutic approach, which maximizes the benefits and limits the adverse events.
Abstract: Introduction: Although the etiology of inflammatory bowel diseases (IBD) remains unknown, accumulating evidence suggests that the intestinal tissue damage in these disorders is due to a dynamic interplay between immune cells and non-immune cells, which is mediated by cytokines produced within the inflammatory microenvironment. Areas covered: We review the available data about the role of inflammatory cytokines in IBD pathophysiology and provide an overview of the therapeutic options to block the function of such molecules. Expert opinion: Genome studies, in vitro experiments with patients' samples and animal models of colitis, have largely advanced our understanding of how cytokines modulate the ongoing mucosal inflammation in IBD. However, not all the cytokines produced within the damaged gut seem to play a major role in the amplification and perpetuation of the IBD-associated inflammatory cascade. Indeed, while some of the anti-cytokine compounds are effective in some subgroups of IBD patients, others have no benefit. In this complex scenario, a major unmet need is the identification of biomarkers that can predict response to therapy and facilitate a personalized therapeutic approach, which maximizes the benefits and limits the adverse events.
89 citations
TL;DR: Complement inhibition by gene therapy will be explored in the phase 1 trial of HMR59 in AMD patients, and complement inhibition has not yet demonstrated the ability to halt GA progression in a phase 3 trial.
Abstract: Introduction: Dry age-related macular degeneration (AMD) and Stargardt Macular Dystrophy (STGD1) result in vision loss due to progressive atrophy of the macula and lack of effective treatments. Num...
69 citations
TL;DR: Gelatin, a collagen-derived natural biopolymer, has been extensively used in regenerative medicine applications over the years, due to its cell-responsive properties and the capacity to deliver a wide range of biomolecules.
Abstract: Introduction: Biomaterials have provided a wide range of exciting opportunities in tissue engineering and regenerative medicine. Gelatin, a collagen-derived natural biopolymer, has been extensively...
67 citations
TL;DR: This review covered the current and novel biological agents used in the management of diabetes-induced osteoporosis and found biological medications that effectively decrease hyperglycemia and maintain bone health would be an ideal drug/drug combination for the treatment of DM-OS.
Abstract: Introduction: Currently, 424 million people aged between 20 and 79 years worldwide are diabetic. More than 25% of adults aged over 65 years in North America have Type 2 diabetes mellitus (D...
66 citations
TL;DR: Targeted BCMA-based immunotherapies used earlier in the disease course and in combination have great promise to achieve long-term disease control and potential cure.
Abstract: Introduction: B cell maturation antigen (BCMA) contributes to MM pathophysiology and is a target antigen for novel MM immunotherapy. Complete responses have been observed in heavily pretreated MM patients after treatment with BCMA antibody-drug conjugates (ADC), chimeric antigen receptor T, and bi-specific T cell engagers (BiTE®). These and other innovative BCMA-targeted therapies transform the treatment landscape and patient outcome in MM. Areas covered: The immunobiological rationale for targeting BCMA in MM is followed by key preclinical studies and available clinical data on efficacy and safety of therapies targeting BCMA from recent phase I/II studies. Expert opinion: BCMA is the most selective MM target antigen, and BCMA-targeted approaches have achieved high responses even in relapse and refractory MM as a monotherapy. Long-term follow-up and correlative studies using immuno-phenotyping and -sequencing will delineate mechanisms of overcoming the immunosuppressive MM bone marrow microenvironment to mediate additive or synergistic anti-MM cytotoxicity. Moreover, they will delineate cellular and molecular events underlying the development of resistance underlying relapse of disease. Most importantly, targeted BCMA-based immunotherapies used earlier in the disease course and in combination (adoptive T cell therapy, mAbs/ADCs, checkpoint and cytokine blockade, and vaccines) have great promise to achieve long-term disease control and potential cure.
58 citations
TL;DR: The development and approval of the IL-17 inhibitor agents secukinumab, ixekizuab, and brodalumab has expanded psoriatic treatment with effective options, validating the importance of the pro-inflammatory role of IL- 17 psoriasis pathophysiology.
Abstract: Introduction: Interleukin-17 (IL-17) is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of plaque psoriasis. As a result, focus in clinical trials has und...
57 citations
TL;DR: SVF provides a cellular and molecular microenvironment for regulation of ASC’ activities under different clinical conditions and novel point of care methods are emerging to refine SVF in ways that meet the regulatory requirements for minimal manipulation.
Abstract: Introduction: The heterogeneous pool of cells found in the stromal vascular fraction of adipose tissue (SVF) and the purified mesenchymal stromal/stem cells (ASCs) isolated from this pool have increasingly been used as therapeutic tools in regenerative medicine.Areas covered: As SVF and ASCs are different, and should be used in different manners according to various clinical and biological indications, we reviewed the current literature, and focused on the clinical use of SVF to appraise the main medical fields for development. Both enzymatic digestion and mechanical disruption have been used to obtain SVF for non-homologous use. The safety and/or benefits of SVF have been examined in 71 clinical studies in various contexts, mainly musculoskeletal conditions, wound healing, urogenital, and cardiovascular and respiratory diseases. The use of SVF as a therapy remains experimental, with few clinical trials.Expert opinion: SVF provides a cellular and molecular microenvironment for regulation of ASC' activities under different clinical conditions. SVF may enhance angiogenesis and neovascularization in wound healing, urogenital and cardiovascular diseases. In joint conditions, therapeutic benefits may rely on paracrine immune-modulatory and anti-inflammatory mechanisms. Novel point of care methods are emerging to refine SVF in ways that meet the regulatory requirements for minimal manipulation.
55 citations
TL;DR: Takeaway: All four CGRP mAbs demonstrated an excellent safety, tolerability and efficacy profile in migraine patients and are likely to usher in a new era in migraine prevention and provide significant value to patients.
Abstract: Introduction: Calcitonin Gene-Related Peptide (CGRP) plays a crucial role in migraine pathophysiology. A novel specific treatment strategy for the prevention of migraine incorporates monoclonal antibodies (mAbs) against CGRP and its canonical receptor. Eptinezumab, fremanezumab and galcanezumab block CGRP mediated effects by binding to the peptide, while erenumab blocks the CGRP receptor.Areas covered: Following a brief overview of pharmacological characteristics, we will review phase III trials for the use of CGRP mAbs in the prevention of episodic and chronic migraine.Expert opinion: All four CGRP mAbs demonstrated an excellent safety, tolerability and efficacy profile in migraine patients. Across all trials mAbs showed superior efficacy for the reduction of monthly migraine days compared to placebo with a net benefit of 2.8 days. Neither cardiovascular nor immunological safety concerns have emerged from clinical trials. Fremanezumab, galcanezumab, and erenumab are approved in the USA and Europe. Based on trial data there is no reason why these mAbs should not become first-line therapies in future. For now, we advocate for the use of mAbs in migraine prevention for patients who failed a minimum of two standard oral treatments based on the novelty and costs of this approach. mAbs are also effective in patients with medication overuse and with comorbid depression or anxiety disorders. Taken together, mAbs are likely to usher in a new era in migraine prevention and provide significant value to patients.
49 citations
Claude Bernard University Lyon 11, Paris Diderot University2, University of Paris3, Paris Descartes University4, Necker-Enfants Malades Hospital5, University of Grenoble6, Quinze-Vingts National Eye Hospital7, Aix-Marseille University8, Centre national de la recherche scientifique9, University of Lyon10
TL;DR: The present work was led by a multidisciplinary panel of experts, including internal medicine specialists, rheumatologists and ophthalmologists, and proposes an extensive review on the use of biological agents in non-infectious uveitis.
Abstract: Introduction: Conventional immunosuppressive drugs, anti-TNF alpha treatments and biotherapies are increasingly being used in non-infectious uveitis.Areas covered: The present work was led by a mul...
49 citations
TL;DR: This review aims to give the reader a complete and updated overview of hormonal and biological therapies for the treatment of endometriosis, underlining the latest developments in this field of research.
Abstract: Introduction: Endometriosis is a chronic benign estrogen-dependent disease characterized by the presence of endometriotic glands and stroma outside the uterine cavity. Although combined hormonal co...
TL;DR: Although some factors, such as a high mutation rate, favor immunotherapy for SCLC patients, downregulation of MHC class I, low expression of PD-L1, poor tumor infiltration by effector T cells, presence of myeloid-derived suppressor cells as well as regulatory T lymphocytes counteract the immune system activation by checkpoint inhibitors.
Abstract: Introduction: Small cell lung cancer (SCLC) is a highly malignant disease with a dismal prognosis that is currently being tested for theclinical activity of checkpoint inhibitors. SCLC is associate...
TL;DR: Mechanisms of action, efficacy, safety, and tolerance of anti-CD20 therapies for MS, including rituximab, ocrelizumab, and ofatumumab are reviewed.
Abstract: Introduction: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The latest development of B-cell depletion by anti-CD20 monoclonal antibodies has been a large...
TL;DR: This study confirmed the effectiveness and safety of secukinumab in real-world patients with psoriasis and had comparable effectiveness in biologic naïve and non-naïve patients.
Abstract: Background: Long term data on the real-life use of secukinumab are scant. The aim of this study was to investigate the real-life effectiveness, safety and treatment persistence of secukinum...
TL;DR: Clinical evidence for different immunotherapeutic approaches for NPC is reviewed, including adoptive cellular therapy, therapeutic cancer vaccines, and immune checkpoint inhibitors, and the development of scalable and reproducible immune product generation processes.
Abstract: Introduction: Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Epstein-Barr virus (EBV) represents a unique etiological culprit in the poorly differentiated nonkeratinizing and undifferentiated subtypes. EBV antigens are expressed on tumor cells albeit in a restricted manner. Treatment options for recurrent or metastatic disease are limited. Nevertheless, emerging data from immunotherapy studies in NPC have shed light into their potential antitumor efficacy. Areas covered: This article reviews existing clinical evidence for different immunotherapeutic approaches for NPC, including adoptive cellular therapy, therapeutic cancer vaccines, and immune checkpoint inhibitors. Expert opinion: There is a growing understanding on EBV virology and the immune evasion mechanisms in NPC. Immunotherapeutic strategies leveraging these properties have shown encouraging efficacy and safety results in early-phase clinical studies. Moving forward, areas to be addressed include appropriate patient selection, optimal incorporation into standard treatment paradigms, biomarker identification, as well as the development of scalable and reproducible immune product generation processes.
TL;DR: It is demonstrated that MCLA-117 efficiently redirects T cells to kill tumour cells while sparing the potential of the bone marrow to develop the full hematological compartment and support further clinical evaluation as a potentially potent treatment option for AML.
Abstract: Objective: We report the characterization of MCLA-117, a novel T cell-redirecting antibody for acute myeloid leukaemia (AML) treatment targeting CD3 on T cells and CLEC12A on leukaemic cell...
TL;DR: Gene therapy is still in its infancy with respect to LSDs, however, efficacy and safety has been demonstrated in numerous pre-clinical studies, and promising clinical results suggest that gene therapy treatment for several LSDs is a real possibility.
Abstract: Introduction: Gene therapies can be envisioned for many disorders where conventional therapies fall short. Lysosomal Storage Disorders (LSDs) are inherited, mostly monogenic, disorders resulting fr...
TL;DR: The recently established therapeutic targeting of B cells in MS patients using CD20 monoclonal antibodies (CD20-mAbs) not only profoundly suppresses inflammatory disease activity but also materializes as the first treatment approach against disability accumulation in a subset of patients with primary progressive MS.
Abstract: Introduction: Featuring demyelination and axonal degeneration, multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system representing a prominent cause of disability in ...
TL;DR: Tocilizumab, the only anti-IL-6-receptor antagonist currently available for AOSd, has proved to be effective for the management of refractory AOSD patients, including those with life-threatening complications.
Abstract: Introduction: Adult-onset Still´s disease (AOSD) is a systemic inflammatory condition that affects mainly young people. The clinical course consists of two distinctive patterns: one with a predomin...
TL;DR: This review summarizes the advances made on poxvirus oncolytic virotherapy in the last five years and predicts that this new modality will continue to improve as an adjunct biotherapy to treat malignant diseases.
Abstract: Introduction: Over the last decade, advances in biological therapies have resulted in remarkable clinical responses for the treatment of some previously incurable cancers. Oncolytic virotherapy is ...
TL;DR: Adalimumab biosimilars will be used to greater extent than etanercept or infliximab to treat patients with moderate-to-severe psoriasis and multiple-switch studies are intended to provide evidence in support of FDA-required interchangeability.
Abstract: Introduction: Biosimilars are biological products that are very similar to their originators, with no meaningful differences in terms of efficacy, safety, and purity. Since the patents of some of t...
TL;DR: This review will focus on the rationale of the blockade of IL-12/23 axis in CD, efficacy and safety data of ustekinumab derived from randomized controlled trials and real-life observational studies, and the preliminary data of the highly promising selective IL-23 inhibitors.
Abstract: Introduction: Blockers of IL-12/23, as well as specific blockers of IL-23, have been investigated as options for medical therapy in inflammatory bowel disease. These biological agents include ustek...
TL;DR: It is crucial that HIF-activation is combined with cell protective strategies and prevascularization techniques to obtain fully vascularized, vital tissues of therapeutically relevant dimensions.
Abstract: Introduction: Vascularization remains one of the greatest yet unmet challenges in tissue engineering. When engineered tissues are scaled up to therapeutically relevant dimensions, their demand of o...
TL;DR: More research is needed to establish its efficacy in different disease stages and applicability in other tumor types, and prospective, randomized trials of durvalumab, alone and/or in combination with other agents, will bring answers to these questions in the near future.
Abstract: Introduction: The U.S. FDA has approved durvalumab for the treatment of advanced urothelial and non-small cell lung cancers. However, this immunotherapy agent is also being explored in other cancers. There is also ongoing research to better predict the responses to this drug. Areas covered: We summarize the literature regarding durvalumab pharmacology, safety and efficacy in several tumor types. We searched PubMed/Medline database from inception to 20 April 2019, performed a snowball method, and visited independent websites such as the U.S. FDA ( https://www.fda.gov ), ClinicalTrials.gov, among others. Expert opinion: Advanced phase clinical trials have shown benefit of durvalumab in advanced urothelial and non-small cell lung cancers, and suggest benefit in several other tumor types. This agent has a tolerable toxicity profile and seems more effective in patients with a higher PDL-1 expression, although this correlation is not perfect. An improved method to predict a response to durvalumab would be beneficial to best tailor therapy and minimize medical care costs. More research is needed to establish its efficacy in different disease stages and applicability in other tumor types. Hopefully, prospective, randomized trials of durvalumab, alone and/or in combination with other agents, will bring answers to these questions in the near future.
TL;DR: In this paper, the authors compared the pharmacokinetics of Sandoz biosimilar adalimumab (GP2017) with reference ADALUMAB (Humira) in healthy volunteers.
Abstract: Background: To compare the pharmacokinetics of Sandoz biosimilar adalimumab (GP2017) with reference adalimumab (Humira) in healthy volunteers (PK similarity study) and to compare the pharmacokineti...
TL;DR: Secukinumab represents the first anti-IL-17A agent available for the treatment of ankylosing spondylitis, with evidence of efficacy upon signs and symptoms of the disease, even after anti-TNF failure, and acceptable safety profile.
Abstract: Introduction: Ankylosing spondylitis is the prototype of spondyloarthritis, a chronic inflammatory disease involving mainly the axial skeleton. The treatment strategy was, until now, restri...
TL;DR: An overview of the molecular pathology that leads to an increase in Aβ peptide accumulation, of the mechanism of action for antibody mediated therapies and of the therapeutic vaccines that target Aβ under development are provided.
Abstract: Introduction: Alzheimer’s disease looms as a profound and growing threat to future human health. The disease is thought to be primarily driven by aberrant proteolysis of the amyloid precursor prote...
TL;DR: The findings for advanced disease and in the pilot phase II study in early-stage colon cancer open a new avenue for the applicability of immunotherapy in neoadjuvant and adjuvant settings, which are currently under investigation.
Abstract: Introduction: Metastatic colorectal cancer (mCRC) is a challenging disease, whose systemic therapy has traditionally been based on a generalized population of patients, with unsatisfactory clinical outcomes. Immunotherapy has been shown to be efficacious in hypermutated tumors, such as those with microsatellite-instability (MSI-H). Nivolumab, and other immune checkpoint inhibitors (ICI), have recently been evaluated in MSI-H mCRC, with remarkable results.Areas covered: Focused on nivolumab, we aim to present the rationale for the applicability of ICI in MSI-H CRC, and the results of completed phase I/II studies. Ongoing studies, including randomized clinical trials, and perspectives of immunotherapy in clinical scenarios in CRC will be discussed.Expert opinion: Phase I and II clinical trials provide strong evidence for the use of nivolumab and other ICI in the systemic therapy of MSI-H mCRC. Regulatory approvals are restricted to subsequent lines of therapy, but preliminary results in treatment-naive patients are encouraging. The findings for advanced disease and in the pilot phase II study in early-stage colon cancer open a new avenue for the applicability of immunotherapy in neoadjuvant and adjuvant settings, which are currently under investigation. With the exception of POLE-mutated patients, there is little evidence for the use of immunotherapy in MSS patients.
TL;DR: Clinical developments are expected, comprising 1) combination therapies of new agents with cytotoxic chemotherapies; 2) ‘novel-novel’ combinations; 3) immune therapies, including chimeric antigen receptor T-cell therapy; and 4) predictive marker analysis.
Abstract: Introduction: Peripheral T-cell lymphoma (PTCL) is a relatively rare, heterogeneous group of mature T-cell neoplasms generally associated with poor prognosis, partly because of refractoriness again...
TL;DR: The immunotherapy toolbox is rapidly expanding and improving, and the future promises further breakthroughs in the T cell ACT field, however the heterogeneity of the tumor microenvironment and the multiplicity of tumor immune escape mechanisms pose formidable challenges to successful T cell immunotherapy in solid tumors.
Abstract: Introduction: In recent years, immunotherapy for the treatment of solid cancer has emerged as a promising therapeutic alternative. Adoptive cell therapy (ACT), especially T cell-based, has been fou...