| 1. |
- Berglund, S., et al.
(författare)
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Advances in umbilical cord blood cell therapy : the present and the future
- 2017
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Ingår i: Expert Opinion on Biological Therapy. - : Taylor & Francis. - 1471-2598 .- 1744-7682. ; 17:6, s. 691-699
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Umbilical cord blood (UCB), previously seen as medical waste, is increasingly recognized as a valuable source of cells for therapeutic use. The best-known application is in hematopoietic stem cell transplantation (HSCT), where UCB has become an increasingly important graft source in the 28 years since the first umbilical cord blood transplantation (UCBT) was performed. Recently, UCB has been increasingly investigated as a putative source for adoptive cell therapy. Areas covered: This review covers the advances in umbilical cord blood transplantation (UCBT) to overcome the limitation regarding cellular dose, immunological naivety and additional cell doses such as DLI. It also provides an overview regarding the progress in adoptive cellular therapy using UCB. Expert opinion: UCB has been established as an important source of stem cells for HSCT. Successful strategies to overcome the limitations of UCBT, such as the limited cell numbers and naivety of the cells, are being developed, including novel methods to perform in vitro expansion of progenitor cells, and to improve their homing to the bone marrow. Promising early clinical trials of adoptive therapies with UCB cells, including non-immunological cells, are currently performed for viral infections, malignant diseases and in regenerative medicine.
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| 2. |
- Brännström, Mats, 1958
(författare)
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Womb transplants with live births: an update and the future
- 2017
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Ingår i: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 17:9, s. 1105-1112
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Absolute uterine factor infertility, with a uterine absence or presence of a nonfunctional uterus, has during the last decades been the only remaining, major group of female infertility. Uterus transplantation (UTx) has now emerged as the first therapy for these women that have traditionally been regarded as unconditionally infertile.Areas covered: This review summarizes the research preparations in several experimental animal species that paved the way for the clinical introduction of UTx. The article also describes the human UTx attempts that have been reported up until today and the several live births that have occurred after the initial UTx baby was born in 2014. Future developments in human UTx and efforts to create a bioengineered uterus are also discussed.Expert opinion: UTx has already at this early phase of experimental introduction in the human setting proved to be a highly effective treatment for absolute uterine factor infertility. The UTx procedure has now been introduced at several centers worldwide within clinical research studies and with variations in techniques. The outcome and data from these studies will further optimize the UTx procedure to become a safe and highly effective infertility treatment.
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| 3. |
- Di Giuseppe, D., et al.
(författare)
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Uptake of rheumatology biosimilars in the absence of forced switching
- 2018
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Ingår i: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 18:5, s. 499-504
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Tidskriftsartikel (refereegranskat)abstract
- Background: To describe the uptake and system-level effects of the introduction of biosimilars in a setting without forced switching.Research design and methods: We used data from the Swedish Rheumatology Quality register from start of marketing of infliximab (Remsima (R) and Inflectra (R)) and etanercept (Benepali (R)) biosimilars until 31 December 2016. We compared users of each originator-product and its biosimilar(s) by line of treatment: bDMARD-naive patients, non-medical switchers (vs. matched patients remaining on originator), and patients switching from a previous bDMARD of another type.Results: From the start of marketing 1343 patients started an infliximab biosimilar (22 months) and 2691 started etanercept (9months). Overall, the introduction of these biosimilars resulted in an increase of the total number of ongoing infliximab and etanercept treatments (originator + biosimilar) . At the end of the study period, biosimilars accounted for 31% of all infliximab treatments and 31% of all etanercept-treated patients. For each line of therapy, we noted only small differences in patient characteristics between those starting the originator product vs. its biosimilar(s).Conclusions: Introduction of biosimilars have effects beyond replacement of the originator product, in terms of an increased rate of bDMARD initiation. Selection to non-medical switching displayed no particular disease- or patient-characteristics.
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| 4. |
- Larsson, Olivia, et al.
(författare)
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Novel strategies for the treatment of grass pollen-induced allergic rhinitis
- 2016
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Ingår i: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 16:9, s. 1143-1150
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Allergic rhinitis (AR) affects over 20% of the population of Europe and the United States. Allergen immunotherapy (AIT) is currently the only form of treatment that affects symptoms and modifies the progression of disease. Established forms of AIT include subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and are widely effective, yet only 2-9% of eligible patients undergo therapy, likely due to the long duration of treatment. As a result, novel, faster forms of AIT are currently under development. Areas covered: This article provides an overview of AR and summarises the efficacy and mechanisms of established forms of AIT, highlighting the current drawbacks. We discuss novel strategies of AIT that have been developed in an attempt to tackle these limitations, including epicutaneous, intradermal and intralymphatic immunotherapy (ILIT), focusing on ILIT, the treatment that has been most comprehensively assessed. Expert opinion: Current strategies to treat AR suffer from a poor safety profile and, importantly, lack of adherence. ILIT is a faster and safer form of AIT, with a treatment regime of only 12 weeks. Further validation is required, but ILIT, with its short and comparatively inexpensive protocol, has the potential to offer disease-modifying therapy to a larger number of patients.
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| 5. |
- Ludvigsson, Johnny
(författare)
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GAD65: a prospective vaccine for treating Type 1 diabetes?
- 2017
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Ingår i: Expert Opinion on Biological Therapy. - : TAYLOR & FRANCIS LTD. - 1471-2598 .- 1744-7682. ; 17:8, s. 1033-1043
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Forskningsöversikt (refereegranskat)abstract
- Introduction: In spite of modern techniques, the burden for patients with type 1 diabetes (T1D) will not disappear and T1D remains a life-threatening disease causing severe complications and increased mortality. We have to learn how to preserve residual insulin secretion or even increase beta cell regeneration. This would give a milder disease, simpler treatment and perhaps even cure. Thus, there are good reasons to try therapies that may preserve beta cell function.Areas covered: In this review the author reviews the literature and registered ongoing trials using GAD-alum put in relation to the high number of published different immune interventions.Expert opinion: GAD-alum treatment is safe, tolerable and easy for the patients and healthcare. It seems probable that treatment with GAD65-alum 20 mu g sc can preserve residual beta cell function in T1D, but efficacy needs to be improved. This may be achieved by the use of combination therapies and new approaches for administration.
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| 6. |
- Lässer, Cecilia, 1981
(författare)
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Exosomes in diagnostic and therapeutic applications: biomarker, vaccine and RNA interference delivery vehicle
- 2015
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Ingår i: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 15:1, s. 103-117
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Cells release extracellular vesicles to their surroundings to communicate with each other. Exosomes are a subgroup of 30 – 100-nm-sized extracellular vesicles, originating from the endocytic pathway. They contain RNA molecules, proteins and lipids that can be transferred between cells. Exosomes have been found in several body fluids, indicating that this is a frequently used and tolerated system for cells to communicate RNA molecules and proteins over distances. Areas covered: It has been shown that patients with cancer have higher concentrations of exosomes in their blood and that these exosomes can carry tumor-specific molecules. Exosomes are, therefore, currently being evaluated for their potential use as biomarkers. Additionally, exosomes have been demonstrated to have the capacity to modulate immune responses. Therefore, exosomes are believed to be beneficial as a cell-free vaccine for cancer and infections. Further, as exosomes are the body’s endogenous system for transport RNA, exosomes are also evaluated for their potential use as a therapeutic RNA delivery system. This review provides an overview of studies reporting diagnostic and therapeutic potential for exosomes. Expert opinion: The data reviewed here suggest that exosomes have the potential to be used for both diagnosis and therapy for several diseases in the future.
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| 7. |
- Magalhaes, Isabelle, et al.
(författare)
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Facing the future : challenges and opportunities in adoptive T cell therapy in cancer
- 2019
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Ingår i: Expert Opinion on Biological Therapy. - : Taylor & Francis Group. - 1471-2598 .- 1744-7682. ; 19:8, s. 811-827
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Tidskriftsartikel (refereegranskat)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 found to cause tumor regression and even cure in a percentage of treated patients. Checkpoint inhibitors further underscore the potential of the T cell compartment in the treatment of cancer. Not all patients respond to these treatments; however, many challenges remain.AREAS COVERED: This review covers the challenges and progress in tumor antigen target identification and selection, and cell product manufacturing for T cell ACT. Tumor immune escape mechanisms and strategies to overcome those in the context of T cell ACT are also discussed.EXPERT OPINION: The immunotherapy toolbox is rapidly expanding and improving, and the future promises further breakthroughs in the T cell ACT field. 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, however. Individualized approaches and strategies combining treatments targeting different immunotherapeutic aspects will be needed in order to expand the applicability and improve the response rates in future.
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| 8. |
- Mazzini, Letizia, et al.
(författare)
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Advances in stem cell therapy for amyotrophic lateral sclerosis
- 2018
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Ingår i: Expert Opinion on Biological Therapy. - : Informa UK Limited. - 1471-2598 .- 1744-7682. ; 18:8, s. 865-881
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive, incurable neurodegenerative disease that targets motoneurons. Cell-based therapies have generated widespread interest as a potential therapeutic approach but no conclusive results have yet been reported either from pre-clinical or clinical studies. Areas covered: This is an integrated review of pre-clinical and clinical studies focused on the development of cell-based therapies for ALS. We analyze the biology of stem cell treatments and results obtained from pre-clinical models of ALS and examine the methods and the results obtained to date from clinical trials. We discuss scientific, clinical, and ethical issues and propose some directions for future studies. Expert opinion: While data from individual studies are encouraging, stem-cell-based therapies do not yet represent a satisfactory, reliable clinical option. The field will critically benefit from the introduction of well-designed, randomized and reproducible, powered clinical trials. Comparative studies addressing key issues such as the nature, properties, and number of donor cells, the delivery mode and the selection of proper patient populations that may benefit the most from cell-based therapies are now of the essence. Multidisciplinary networks of experts should be established to empower effective translation of research into the clinic.
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| 9. |
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| 10. |
- Parodis, Ioannis, et al.
(författare)
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Smoking reduces the efficacy of belimumab in mucocutaneous lupus.
- 2018
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Ingår i: Expert Opinion on Biological Therapy. - : Informa Healthcare. - 1471-2598 .- 1744-7682. ; 18:8, s. 911-920
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Recently, we demonstrated a negative impact of smoking on belimumab efficacy in patients with systemic lupus erythematosus (SLE). Here, we particularly investigated clinical effects of belimumab and a potential impact of smoking in mucocutaneous and articular SLE.METHODS: We surveyed 62 SLE patients treated between 2011 and 2017. Evaluation included the mucocutaneous descriptors of SLEDAI-2K (rash, alopecia, mucosal ulcers; mcSLEDAI-2K), CLASI, the arthritis SLEDAI-2K descriptor (arSLEDAI-2K) and the 28-joint count.RESULTS: mcSLEDAI-2K and CLASI activity decreased from baseline to month 6 and 12 (P<0.001 for all). No worsening in CLASI damage was observed. Current or previous smokers displayed a higher probability of unchanged/worsened mcSLEDAI-2K compared to never smokers (OR: 6.4; 95% CI: 1.5-27.4; P=0.012), also after adjustment for antimalarial agents. arSLEDAI-2K scores had decreased at month 6 (P<0.001) and 12 (P<0.001). Likewise, tender and swollen 28-joint counts had improved at month 6 (P=0.010 and P<0.001, respectively) and 12 (P=0.001 for both). We observed no impact of smoking on belimumab efficacy in articular SLE.CONCLUSION: We observed a negative impact of smoking on the efficacy of belimumab in mucocutaneous SLE. In contrast, no impact of smoking on belimumab efficacy was seen in patients with articular manifestations.
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| 11. |
- Magnusson, Kristina, 1979-, et al.
(författare)
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ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer
- 2016
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Methods: Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. Results: High nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1. Conclusions: ANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.
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