Showing papers in "Expert Opinion on Biological Therapy in 2009"
TL;DR: The potential use of miRNAs as clinically diagnostic biomarkers of various cancers and other diseases are discussed as well as the approaches used to detect these molecules in serum and plasma.
Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level by degrading or blocking translation of messenger RNA (mRNA) targets. MiRNAs play important regulatory roles in a variety of cellular functions as well as in several diseases, including cancer. MiRNA-specific expression profiles have been reported for several pathological conditions. Recently, the discovery of miRNAs in serum opens up the possibility of using miRNAs as biomarkers of disease. In this review, we discuss the potential use of miRNAs as clinically diagnostic biomarkers of various cancers and other diseases as well as the approaches used to detect these molecules in serum and plasma.
396 citations
TL;DR: Since ADSCs are easily obtained in large quantities and have an advantage over other stem cell sources, ADSCs and their secretory factors show promise for use in skin repair and regeneration.
Abstract: Background: The aim of tissue engineering is to repair and regenerate damaged organs using a combination of cells, biomaterials and growth factors. Mesenchymal stem cells within the stromal–vascula...
246 citations
TL;DR: The existing experimental literature that has tested the use of MSC in models of ALI/ARDS is described, and the potential mechanisms underlying their therapeutic use are described with an emphasis on secreted paracrine soluble factors.
Abstract: Despite extensive research into the pathogenesis of acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), mortality remains high at approximately 40%. Current treatment is primarily supportive, with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in experimental studies have not yet been translated into effective clinical treatment options. Therefore, innovative therapies are needed. Recent studies have suggested that bone-marrow-derived multipotent mesenchymal stem cells (MSC) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, hepatic and acute renal failure. Recently, MSC have been studied in several in vivo models of lung disease. This review focuses on first describing the existing experimental literature that has tested the use of MSC in models of ALI/ARDS, and then the potential mechanisms underlying their therapeutic use with an emphasis on secreted paracrine soluble factors. The review concludes with a discussion of future research directions required for potential clinical trials.
150 citations
TL;DR: Pasteurized fibrinogen concentrate is well tolerated and associated with a low incidence of adverse thrombo-embolic events, and appears to be an early event in seriously bleeding patients, preceding critical levels of platelets or other coagulation factors.
Abstract: Background: Human fibrinogen concentrates have been commercially available for decades for substitution therapy in hypofibrinogenemia, dysfibrinogenemia and afibrinogenemia. Accumulating new data s...
118 citations
TL;DR: The mechanisms involved in inflammation and specifically the IL-1β signals that lead to the progression of insulin resistance and diabetes are summarized.
Abstract: Since having been cloned in 1984, IL-1β has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1β is a regulator of the bo...
117 citations
TL;DR: The mechanisms by which mammalian cells respond to viral infections in normal versus cancer cells are examined and how viruses overcome these responses are illustrated and to illustrate how this knowledge is used to develop physiologically targeted oncolytic viruses.
Abstract: Background: The use of oncolytic viruses for treatment of cancer marks a significant alteration in the battle between host and virus. Viruses are confronted by cellular innate immune responses and contain an armamentarium of immunomodulatory proteins that suppress innate immunity. Tumorigenesis can result in impairment of innate immune responses. Viruses engineered to be vulnerable to normal responses may mediate tumor-specific killing with minimal off-target toxicity. Objective: To examine the mechanisms by which mammalian cells respond to viral infections in normal versus cancer cells and how viruses overcome these responses and to illustrate how this knowledge is used to develop physiologically targeted oncolytic viruses. Methods: Literature describing studies investigating innate responses to virus infections, cancer-specific molecular defects, immunosuppressive viral products and design of oncolytic viruses is extensively reviewed, and pertinent concepts are distilled and developed. Results/conclusio...
115 citations
TL;DR: The mechanisms by which transplanted MSCs influence neurodegenerative diseases can be broadly classified as cellular replacement or paracrine secretion, with the latter subdivided into trophic factor secretion or immunomodulation by cytokines.
Abstract: Background: Stem-cell-based therapy is a promising new approach to handling neurodegenerative diseases. One of the most promising cellular sources is bone-marrow-derived mesenchymal stem cells (MSC...
113 citations
TL;DR: Although many elements of innate and adaptive immunity are associated with control of HIV infection, the specific mechanism(s) by which elite controllers achieve control remain undefined and ongoing studies of elite controllers should facilitate the definition of an effective HIV-specific immune response and guide vaccine design.
Abstract: Background: ‘Elite controllers’ are rare HIV-infected individuals who are able to spontaneously control HIV replication without medication, maintaining viral loads that are consistently below the limits of detection by currently available commercial assays. Objective: To examine studies of elite controllers that may elucidate mechanisms of HIV immune control useful in designing a vaccine. Methods: Recent literature on HIV controllers and studies that have evaluated aspects of viral and host immunology that correlate with viral control are examined. Results/conclusions: Although many elements of innate and adaptive immunity are associated with control of HIV infection, the specific mechanism(s) by which elite controllers achieve control remain undefined. Ongoing studies of elite controllers, including those examining host genetic polymorphisms, should facilitate the definition of an effective HIV-specific immune response and guide vaccine design.
103 citations
TL;DR: In vivo data showed that TGF-β3 cultured with ovine mesenchymal stem cells in a chitosan scaffold stimulated the growth of hyaline cartilage that was fully integrated into host cartilage tissue of sheep.
Abstract: Background: TGF-β has been proposed to stimulate chondrogenesis through intracellular pathways involving small mothers against decapentaplegic proteins (Smads). Objective: To examine the use of exogenous TGF-β3 to promote new hyaline cartilage formation. Methods: An overview of in vitro and in vivo evidence on the effects of TGF-β3 on cartilage regeneration. Results/conclusion: There is robust in vitro evidence suggesting a positive dose- and time-dependant effect of TGF-β3 on anabolic chondrogenic gene markers such as α1-collagen type II and cartilage oligomeric matrix protein in human mesenchymal stem cells. TGF-β3 cultured with silk elastin-like polymer scaffold carrier exhibits significantly increased glycosaminoglycan and collagen content. In vivo data showed that TGF-β3 cultured with ovine mesenchymal stem cells in a chitosan scaffold stimulated the growth of hyaline cartilage that was fully integrated into host cartilage tissue of sheep. We highlight the potential for the clinical enhancement of ca...
103 citations
TL;DR: TachoSil is used in many surgical specialties and has proven to be a valuable tool for several indications and it also seems to be cost effective.
Abstract: Background: Proper haemostasis is an important prerequisite for a successful outcome in all operative fields. TachoSil® is used in many surgical specialties, especially for diffuse bleeding. However, TachoSil is not only used for haemostasis but also for closure of other anatomical structures. Objective: To review the literature concerning the efficacy of TachoSil, a topical fibrin-based haemostat. Methods: PubMed was searched for data on TachoSil and TachoComb from clinical trials and basic research. Results/conclusion: TachoSil is used in many surgical specialties and has proven to be a valuable tool for several indications. It also seems to be cost effective. Solid data from randomized controlled trials are available for liver surgery, thoracic surgery and urology where a positive value is clearly documented.
102 citations
TL;DR: This review outlines and compares the latest development of strategies to inhibit the VEGF pathway, with emphasis on aflibercept, a novel decoy fusion protein of domain 2 of V EGFR-1 and domain 3 of VEGFR-2 with the Fc fragment of IgG1.
Abstract: Background: Aberrant angiogenesis is a landmark feature in cancer, which is important for proliferation, growth and metastasis, and is mediated by various pro-angiogenic factors. The VEGF pathway is one of the most important and best-studied angiogenic pathways. Inhibition of this pathway may provide clinical benefits to cancer patients. Objectives: Strategies to inhibit the VEGF pathway, including antibodies to VEGF, antibodies to the extracellular domain of VEGFR-1 or VEGFR-2, decoy receptors for VEGF and tyrosine kinase inhibitors of VEGFRs, are summarized. Methods: This review outlines and compares the latest development of these strategies, with emphasis on aflibercept, a novel decoy fusion protein of domain 2 of VEGFR-1 and domain 3 of VEGFR-2 with the Fc fragment of IgG1. Results: Aflibercept was shown to have early clinical activity. Multiple studies are ongoing to determine the clinical benefits of aflibercept in cancer patients.
TL;DR: This review highlights the current understanding of cellular and molecular responses of ASCs to hypoxia, focusing on the enhancement of ASC function and secretory activity by hypoxic culture conditions.
Abstract: Mesenchymal stem cells within the stromal-vascular fraction of subcutaneous adipose tissue (i.e., adipose-derived stem cells (ASCs)), have been used for tissue engineering. In addition to serving a building-block function, ASCs are reported to secrete growth factors that are essential for their function. Increasing evidence indicates that ASCs play a significant role in skin regeneration, a function that is enhanced by hypoxia through upregulating secretion of growth factors. Although the anatomical sites of ASCs in the body are relatively oxygen-deficient, ASCs are usually cultured under normoxic conditions (i.e., atmospheric oxygen levels). Culturing ASCs under physiologically relevant low-oxygen-tension conditions may uniquely benefit the expansion, differentiation, adhesion, growth factor secretion and regenerative potential of ASCs. Therefore, understanding the response and adaptation of ASCs to hypoxia may be invaluable for developing novel cell- and cyto-therapy strategies. This review highlights our current understanding of cellular and molecular responses of ASCs to hypoxia, focusing on the enhancement of ASC function and secretory activity by hypoxic culture conditions.
TL;DR: Current understanding of B-cell therapy, the role of rituximab in the treatment of RA and the evolving role of ocrelizumab, a novel humanized anti-CD20 antibody, are described.
Abstract: Recent advances in our understanding of B-cell dysregulation and its important link to autoimmunity have brought about a radical change in the management of autoimmune diseases. Over the past few years, encouraging data from several clinical trials of rituximab, a chimeric anti-CD20 antibody, have led to its approval for use in rheumatoid arthritis (RA). These data, regarding clinical efficacy, safety, improved patient-reported outcomes and cost-effectiveness with the use of rituximab in patients with RA, have led to the exploration of other agents targeting B-cell functions. Ocrelizumab, a novel humanized anti-CD20 antibody, has shown clinical efficacy and safety in a recently reported trial in patients with RA. Future clinical trials will help evaluate further the role of ocrelizumab in RA and its potential use in other autoimmune diseases. This review describes current understanding of B-cell therapy, the role of rituximab in the treatment of RA and the evolving role of ocrelizumab as a B-cell-targeted...
TL;DR: There are many potential uses for denileukin diftitox, in both malignant and benign disorders, and more human trials are needed to demonstrate further efficacy for a wide range of diseases.
Abstract: Objective: To review FDA approved and other potential uses of Ontak, denileukin diftitox. Methods: Information was obtained via the internet and a journal literature review. Results: In 1999, the FDA approved the use of denileukin diftitox for patients with persistent or relapsed CD25-positive cutaneous T-cell lymphoma (CTCL), but Ontak has been reported to be an effective therapy for other neoplastic and non-neoplastic conditions. Oncological uses include therapy for CD25-negative T-cell lymphoma, recurrent and refractory chronic lymphocytic leukemia (CLL), non-Hodgkin's B-cell lymphoma (NHL), and human T-cell lymphotropic virus- 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL). Potential additional uses of Ontak include: therapy of graft-versus-host disease (GvHD) and autoimmune conditions, including psoriasis, rheumatoid arthritis (RA), systemic lupus, scleroderma and vasculitis. Denileukin diftitox's effect has also been studied for patients with hepatocellular carcinoma (HCC) and HIV, but c...
TL;DR: The mimotope concept is applicable to both fields for epitope-specific vaccination and analysis of conformational B-cell epitopes for the allergen/antigen.
Abstract: Background: Mimotopes are peptides mimicking protein, carbohydrates or lipid epitopes and can be generated by phage display technology. When selected by antibodies, they represent exclusively B-cell epitopes and are devoid of antigen/allergen-specific T-cell epitopes. Coupled to carriers or presented in a multiple antigenic peptide form mimotopes achieve immunogenicity and induce epitope-specific antibody responses upon vaccination. Objective/methods: In allergy IgG antibodies may block IgE binding to allergens, whereas other IgG antibody specificities enhance this and support the anaphylactic reaction. In cancer, inhibitory antibody specificities prevent growth signals derived from overexpressed oncogenes, whereas growth-promoting specificities enhance signalling and proliferation. Therefore, the mimotope concept is applicable to both fields for epitope-specific vaccination and analysis of conformational B-cell epitopes for the allergen/antigen. Results/conclusions: Mimotope technology is a relatively yo...
TL;DR: Nimotuzumab, a humanized murine mAb created in Cuba, has demonstrated antitumor activity similar to that of other anti-EGFR mAbs and shows promise as a single agent and as an adjunct to radiation in Phase I and II clinical trials.
Abstract: Due to the broad importance of EGFR to tumorogenesis, targeted therapy against it has rapidly developed into a novel paradigm for cancer treatment Two promising classes of drugs are now in use and undergoing development that target this receptor: tyrosine kinase inhibitors (TKIs) and mAbs that inhibit EGFR's extracellular domain Nimotuzumab, a humanized murine mAb created in Cuba, has demonstrated antitumor activity similar to that of other anti-EGFR mAbs and shows promise as a single agent and as an adjunct to radiation in Phase I and II clinical trials Surprisingly, the typical severe dermatological toxicities thus far associated with anti-EGFR therapy have not been described with nimotuzumab Here we summarize the background, development and characteristics of this new drug while reviewing the latest preclinical and clinical trial data that underpin its gradual adoption into clinical practice
TL;DR: Recent advances in- and limitations of each of the approaches to improve the efficacy of Ad-based vaccines, and allow modified vaccines to overcome pre-existing Ad immunity are discussed.
Abstract: Adenovirus (Ad)-based vectors offer several benefits showing their potential for use in a variety of vaccine applications. Recombinant Ad-based vaccines possess potent immunogenic potential, capabl...
TL;DR: The most recent reports of clinical trials with Tα1 are pointing to important, hitherto unrecognized, applications in a number of diseases and disorders, including septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients.
Abstract: Background: Thymosin α1 (Tα1), a synthetic version of a thymic-derived biological response modifier was the first of the thymosins in clinical use. Tα1 is approved in over 35 countries for the treatment of hepatitis B and C, and as an immune stimulant and adjuvant. Tα1 is also in late-stage clinical testing in the United States and Europe for hepatitis C and stage IV melanoma. Objective/methods: Novel applications and other recently completed trials point to much broader clinical applications of Tα1 in the treatment of life-threatening and chronic diseases, and are the subject of this review. Result/conclusions: The most recent reports of clinical trials with Tα1 are pointing to important, hitherto unrecognized, applications in a number of diseases and disorders, including septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients. It is also emerging as a promising chemoprotection a...
TL;DR: These trials demonstrated that a selected population of GBM patients who received vaccines targeting EGFRvIII had an unexpectedly long survival time, and further therapeutic strategies and potential pitfalls of using this approach are discussed.
Abstract: Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, resulting in non-specific toxicity. Immune targeting of tumor-specific mutations may allow for more precise eradication of neoplastic cells. EGFR variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed in GBM and other neoplasms and its expression enhances tumorigenicity. This in-frame deletion mutation splits a codon, resulting in a novel glycine at the fusion junction producing a tumor-specific epitope target for cellular or humoral immunotherapy. We have previously shown that vaccination with a peptide that spans the EGFRvIII fusion junction (PEPvIII-KLH/CDX-110) is an efficacious immunotherapy in syngeneic murine models. In this review, we summarize our results in GBM patients targeting this mutation in multiple, multi-institutional Phase II immunotherapy trials. These trials demonstrated that a selected population of GBM patients who received vaccines targeting EGFRvIII had an unexpec...
TL;DR: It is found that repair tissue from human articular cartilage during the late stages of osteoarthritis harbors a unique progenitors cell population, termed chondrogenic progenitor cells (CPC), which exhibit stem cell characteristics combined with a high chondrogensic potential.
Abstract: Enhancing the regeneration potential of hyaline cartilage tissue remains a great challenge. During embryonic development, some of the cells of the inner cell mass will turn into the mesoderm. This ...
TL;DR: This review discusses the different approaches recently developed in order to induce stronger peptide-induced immune-mediated tumor growth control, possibly translating into improved clinical response rates, with specific focus on multipeptide-based anti-cancer vaccines.
Abstract: Since the identification of tumor associated antigens (TAA) in different tumor histotypes, many vaccination strategies have been investigated, including peptide-based vaccines. Results from the first decade of clinical experimentation, though demonstrating the feasibility and the good toxicity profile of this approach, provided evidence of clinical activity only in a minority of patients, despite inducing immunization in up to 50% of them. In this review, we discuss the different approaches recently developed in order to induce stronger peptide-induced immune-mediated tumor growth control, possibly translating into improved clinical response rates, with specific focus on multipeptide-based anti-cancer vaccines. This strategy offers many advantages, such as the possibility of bypassing tumor heterogeneity and selection of antigen (Ag)-negative clones escaping peptide-specific immune responses, or combining HLA class I- and class II-restricted epitopes, thus eliciting both CD4- and CD8-mediated immune recog...
TL;DR: This review summarizes the reported preclinical and clinical data obtained with the prepandemic H5N1 vaccine adjuvanted with AS03, which allows for antigen sparing, has a good safety and acceptable reactogenicity profile, induces an immune response that not only meets all European Committee for Medicinal Products (CHMP) and FDA requirements for the vaccine strain, and conveys protection in a ferret model against lethal challenges with homologous and heterologous H5n1 viruses.
Abstract: Background: Universal and timely administration of a prepandemic vaccine is considered to be one of the most effective measures to reduce the incidence of pandemic influenza infection and consequently its morbidity and mortality. Objectives: To provide the reader with basic insights into influenza virus infections, the threat of a pandemic and the challenges it poses for vaccine development. Methods: This review summarizes the reported preclinical and clinical data obtained with the prepandemic H5N1 vaccine adjuvanted with AS03. Results: The AS03-adjuvanted prepandemic H5N1 influenza vaccine allows for antigen sparing, has a good safety and acceptable reactogenicity profile, induces an immune response that not only meets all European Committee for Medicinal Products (CHMP) and FDA requirements for the vaccine strain but also generates neutralizing antibodies that broadly cross-react against H5N1 drift strains, and finally conveys protection in a ferret model against lethal challenges with homologous and h...
TL;DR: Bvacizumab has an established role in the treatment of metastatic colon, breast, and lung cancer and many questions remain on its use in other disease types and demographic groups.
Abstract: Background: Angiogenesis is essential for cancer growth and metastasis. VEGF is a key modulator of angiogenesis and its overexpression is correlated with advanced disease and poor prognosis. Bevacizumab, a recombinant humanized anti-VEGF mAb, is the most clinically advanced anti-angiogenic agent. Although bevacizumab has received most attention for first-line treatment of advanced colorectal and non-small-cell lung cancer, there is a rapidly growing body of evidence for its efficacy in treatment of a number of other solid tumors. Objective/methods: We present the background, current status, and important ongoing trials involving the use of bevacizumab therapy. Results/conclusions: Bevacizumab has an established role in the treatment of metastatic colon, breast, and lung cancer. Yet many questions remain on its use in other disease types and demographic groups.
TL;DR: Trastuzumab, a recombinant humanized anti-HER-2 monoclonal antibody, is the first biological therapy that has showed a survival improvement by nearly 3 months (reduced risk of death by 26%), thus trastuzuab in combination with chemotherapy is a treatment option for patients with HER2-positive advanced gastric cancer.
Abstract: Background: Gastric cancer is a disease with different management approaches in different regions, especially between Western and Asian countries. Surgery is the mainstay of treatment for non-metastatic disease. Perioperative chemotherapy or adjuvant radio-chemotherapy is recommended, since recurrences are common after curative resection. Unfortunately, advanced or metastatic gastric cancer constitutes the majority of patients in clinical practice. For these patients systemic chemotherapy is the standard treatment, to provide palliation and prolong survival; however, prognosis remains poor. Several molecular targeting agents are under evaluation in international randomized studies. Objective: To review chemotherapy and targeted therapies for gastric cancer, chemical and pharmacological characteristics of trastuzumab, and evidence for its clinical use in gastric cancer. Methods: Examination of relevant literature. Results/conclusions: HER-2 is overexpressed/amplified in approximately 22% of gastric cancer ...
TL;DR: How VEGF blockade impacts tumor vascular maturation is explored and its implications for cancer therapy is considered.
Abstract: Tumor angiogenesis is an important component of cancer biology driven in part by the thesis that inhibition of tumor vessel growth would be expected to starve and thereby disrupt tumor growth. A significant portion of research on tumor angiogenesis has focused on VEGF and its blockade with the expectation that dramatic results would be demonstrated in cancer patients as previously documented in animal models. However, to date, anti-VEGF (bevacizumab, Avastin) therapy alone has demonstrated little if any antitumor activity or survival benefit in humans. Interestingly, bevacizumab in combination with chemotherapeutic agents appears to result in a modest survival benefit in patients with various malignancies. This has prompted the re-evaluation of the biological effects resulting from VEGF blockade. Recent reports indicate that inhibition of VEGF and its receptor can have dramatic and unexpected effects on mural and perivascular cells in the tumor microenvironment, leading to vascular smooth muscle cell/pericyte activation and vessel normalization/maturation. Specifically, when VEGF levels in tumors are high, recent studies suggest that this leads to reduced responsiveness of the mural cell to the related growth factor, platelet-derived growth factor. This raises the possibility that in addition to the demonstrated anti-angiogenic effect of VEGF neutralization, mural cell recruitment and thus vascular maturation might be among the most critical activities of anti-VEGF agents. This review seeks to explore how VEGF blockade impacts tumor vascular maturation and considers its implications for cancer therapy.
TL;DR: Rilonacept is a recently FDA approved biologic therapy for CAPS with high affinity for IL-1β that produced rapid and profound improvements in symptoms and also reduced high-sesitivity C-reactive protein levels and normalized elevated serum amyloids A concentrations, an important risk factor for amyloidosis.
Abstract: Background: Cryopyrin-associated periodic syndromes (CAPS) encompass a group of rare inherited, autoinflammatory disorders that represent a spectrum of one disease with varying degrees of severity. Until recently, there was no effective treatment for CAPS, but identification of the genetic basis of CAPS highlighted the pathogenic role of IL-1β. Objectives: Rilonacept is a recently FDA approved biologic therapy for CAPS with high affinity for IL-1β. Limited pharmacological data has been reported to date. Methods: A review of the phamacokinetics and pharmacodynamics data as well as the results of a pilot study and Phase III placebo-controlled trials of rilonacept in CAPS. Unpublished data on an open-label extension study in adult and pediatric subjects is also reviewed. Results: Rilonacept produced rapid and profound improvements in symptoms and also reduced high-sesitivity C-reactive protein levels and normalized elevated serum amyloid A concentrations, an important risk factor for amyloidosis. The primary...
TL;DR: Clinical evaluation of reovirus therapy has shown that it is well tolerated when administered locally or systemically and the lack of toxicity and promising efficacy has raised hopes that it will become an established anticancer agent.
Abstract: Reovirus is an oncolytic virus that is not associated with significant disease in humans, but is selectively able to replicate in cancer cells through exploitation of abnormal Ras signaling. Pre-clinical studies have demonstrated that treatment with reovirus is associated with significant anticancer activity across a range of tumor types. Reolysin is a proprietary formulation of the human reovirus developed by Oncolytics Biotech. Clinical evaluation of reovirus therapy has shown that it is well tolerated when administered locally or systemically. Encouraging anticancer efficacy has been observed with single-agent treatment and in combination with chemotherapy and radiotherapy. Phase II studies are currently evaluating reovirus alone and in combination with standard therapy in an array of tumor types. While immune sensitization hinders the anticancer efficacy of reovirus, it is important in preventing systemic toxicity. Immunosuppressive strategies are being developed that reduce immune neutralization of the virus to allow for improved tumor penetration, but retain sufficient antibody levels to protect normal tissues. The lack of toxicity and promising efficacy of reovirus has raised hopes that it will become an established anticancer agent.
TL;DR: New technologies in MR cell tracking will soon take the field beyond preclinical studies and begin to show benefits in clinical trials of novel experimental cell-based therapies.
Abstract: Background: The success of many cell-based therapies is highly dependent on the accurate delivery, dosing and trafficking of the cellular therapeutic. In vivo magnetic resonance (MR) cell tracking provides a means to non-invasively and longitudinally evaluate these parameters for cellular therapy. Objective: To provide an overview of MR cell tracking and how cellular therapeutics might be improved by utilizing this technology. Methods: We focused on the technologies utilized for stem cell and immunotherapies in preclinical models of disease. Results/conclusion: New technologies in MR cell tracking will soon take the field beyond preclinical studies and begin to show benefits in clinical trials of novel experimental cell-based therapies.
TL;DR: There is still considerable uncertainty about the molecular mechanisms through which CD8 Ts cells can reset immune responses to protect the host, but their potential diagnostic and therapeutic use is intriguing and has generated renewed interest.
Abstract: Current treatments for autoimmune disease are hampered by the non-specificity of immunomodulatory interventions, having to accept broad suppression of immunoresponsiveness with potentially serious side effects, such as infection or malignancy. The development of antigen-specific approaches, downregulating pathogenic immune responses while maintaining protective immunity, would be a major step forward. One possible approach involves the targeting of physiological regulatory mechanisms, such as inhibitory CD8 T cells that are now recognized to fine-tune many aspects of immune responses. CD8 T suppressor (Ts) cells may directly inhibit other T cells or condition antigen-presenting cells in such a way that immune amplification steps are dampened. The promise of CD8 Ts cells lies in their potential to disrupt host-injurious immune responses in a targeted fashion. For therapeutic purposes, such CD8 Ts cells could either be generated in vitro and transferred into the host or their numbers and activity could be m...
TL;DR: Acellular aAPCs are a powerful alternative to natural-cell-based therapies, offering flexibility and modularity for incorporation oSf a variety of stimuli, hence increasing precision.
Abstract: Background: Recent findings on T cells and dendritic cells have elucidated principles that can be used for a bottom-up approach to engineering artificial antigen presentation on synthetic substrates. Objective/methods: To compare the latest artificial antigen-presenting cell (aAPC) technology, focussing on acellular systems because they offer advantages such as easy tunability and rapid point-of-care application compared with cellular systems. We review acellular aAPC performance and discuss their promise for clinical applications. Results/conclusion: Acellular aAPCs are a powerful alternative to natural-cell-based therapies, offering flexibility and modularity for incorporation oSf a variety of stimuli, hence increasing precision. Current technologies should adapt physiologically important signals within safe materials to more closely approximate their cellular counterparts. These constructs could be administered parenterally as APC replacements for active vaccines or used ex vivo for adoptive immunotherapy.