An overview of CAR T-cell clinical trial activity to 2021.
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ABSTRACT:
SUBMITTER: Adami A
PROVIDER: S-EPMC8137996 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chimeric antigen receptor (CAR) T-cell therapy exhibits desirable and robust efficacy in patients with acute lymphoblastic leukemia (ALL). Stimulated by the revolutionized progress in the use of FDA-approved CD19 CAR T cells, novel agents with CAR designs and targets are being produced in pursuit of superior performance. However, on the path from bench to bedside, new challenges emerge. Accessibility is considered the initial barrier to the transformation of this patient-specific product into a commercially available product. To ensure infusion safety, profound comprehension of adverse events and proactive intervention are required. Additionally, resistance and relapse are the most critical and intractable issues in CAR T-cell therapy for ALL, thus precluding its further development. Understanding the limitations through up-to-date insights and characterizing multiple strategies will be critical to leverage CAR T-cell therapy flexibly for use in clinical situations. Herein, we provide an overview of the application of CAR T-cell therapy in ALL, emphasizing the main challenges and potential clinical strategies in an effort to promote a standardized set of treatment paradigms for ALL.
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Project description:The 2020-2021 epidemic with a total of 3,555 reported HPAI detections and around 22,400,000 affected poultry birds in 28 European Countries appears to be one of the largest and most devastating HPAI epidemics ever occurred in Europe. Between 24 February and 14 May 2021, 1,672 highly pathogenic avian influenza (HPAI) virus detections were reported in 24 EU/EEA countries and the UK in poultry (n=580), and in wild (n=1,051) and captive birds (n=41). The majority of the detections in poultry were reported by Poland that accounted for 297 outbreaks occurring in a densely populated poultry area over a short period of time, followed by Germany with 168 outbreaks. Germany accounted for 603 detections in wild birds, followed by Denmark and Poland with 167 and 56 detections, respectively. A second peak of HPAI-associated wild bird mortality was observed from February to April 2021 in north-west Europe. The observed longer persistence of HPAI in wild birds compared to previous years may result in a continuation of the risk for juveniles of wild birds and mammals, as well as for virus entry into poultry farms. Therefore, enhanced awareness among farmers to continue applying stringent biosecurity measures and to monitor and report increases in daily mortality and drops in production parameters, are recommended. Sixteen different genotypes were identified to date in Europe and Russia, suggesting a high propensity of these viruses to reassort. The viruses characterized to date retain a preference for avian-type receptors; however, transmission events to mammals and the identification of sporadic mutations of mammal adaptation, indicate ongoing evolution processes and possible increased ability of viruses within this clade to further adapt and transmit to mammals including humans. Since the last report, two human infections due to A(H5N6) HPAI were reported from China and Laos and 10 human cases due to A(H9N2) low pathogenic avian influenza (LPAI) virus identified in China and Cambodia. The risk of infection for the general population in the EU/EEA is assessed as very low and for occupationally exposed people low. People exposed during avian influenza outbreaks should adhere to protection measures, strictly wear personal protective equipment and get tested immediately when developing respiratory symptoms or conjunctivitis within 10 days after exposure.
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Project description:BackgroundCancer is one of the critical issues of the global health system with a high mortality rate even with the available therapies, so using novel therapeutic approaches to reduce the mortality rate and increase the quality of life is sensed more than ever.Main bodyCAR-T cell therapy and oncolytic viruses are innovative cancer therapeutic approaches with fewer complications than common treatments such as chemotherapy and radiotherapy and significantly improve the quality of life. Oncolytic viruses can selectively proliferate in the cancer cells and destroy them. The specificity of oncolytic viruses potentially maintains the normal cells and tissues intact. T-cells are genetically manipulated and armed against the specific antigens of the tumor cells in CAR-T cell therapy. Eventually, they are returned to the body and act against the tumor cells. Nowadays, virology and oncology researchers intend to improve the efficacy of immunotherapy by utilizing CAR-T cells in combination with oncolytic viruses.ConclusionUsing CAR-T cells along with oncolytic viruses can enhance the efficacy of CAR-T cell therapy in destroying the solid tumors, increasing the permeability of the tumor cells for T-cells, reducing the disturbing effects of the immune system, and increasing the success chance in the treatment of this hazardous disease. In recent years, significant progress has been achieved in using oncolytic viruses alone and in combination with other therapeutic approaches such as CAR-T cell therapy in pre-clinical and clinical investigations. This principle necessitates a deeper consideration of these treatment strategies. This review intends to curtly investigate each of these therapeutic methods, lonely and in combination form. We will also point to the pre-clinical and clinical studies about the use of CAR-T cell therapy combined with oncolytic viruses.
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Project description:Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial
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Project description:BackgroundDespite the COVID-19 pandemic, there has been considerable activity in the clinical development of novel and improved drug-based therapies for the neurodegenerative condition of Parkinson's disease (PD) during 2020. The agents that were investigated can be divided into "symptomatic" (alleviating the features of the condition) and "disease modifying" (attempting to address the underlying biology of PD) treatments, ST and DMT respectively, with further categorisation possible based on mechanism of action and class of therapy.ObjectiveOur goal in this report was to provide an overview of the pharmacological therapies -both ST and DMT - in clinical trials for PD during 2020-2021, with the aim of creating greater awareness and involvement in the clinical trial process. We also hope to stimulate collaboration amongst commercial and academic researchers as well as between the research and patient communities.MethodsWe conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov and World Health Organisation (WHO) registries, and performed a breakdown analysis of studies that were active as of February 18th 2021. We also assessed active drug development projects that had completed one clinical phase but were yet to start the next.ResultsWe identified 142 trials on ClinicalTrials.gov and 14 studies on the WHO registries that met our analysis criteria. Of these 156 trials, 91 were ST and 65 were DMT, Of the 145 trials registered on ClinicalTrials.gov in our 2020 analysis, 45 fell off the list and 42 were added. Despite this change, the balance of ST to DMT; the distribution across phases; the profile of therapeutic categories; and the proportion of repurposed therapies (33.5%); all remained very similar. There are only two DMTs in phase 3, and we identified 33 in-between-phase projects.ConclusionsDespite the effects of the coronavirus pandemic, investment and effort in clinical trials for PD appears to remain strong. There has been little change in the profile of the clinical trial landscape even though, over the past year, there has been considerable change to the content of the list.
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Project description:EORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet. Keywords = Apocrine carcinoma Keywords = breast cancer
2005-06-01 | GSE1561 | GEO
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