Platforms for Clinical-Grade CAR-T Cell Expansion.

Platforms for Clinical-Grade CAR-T Cell Expansion. Methods Mol Biol. 2020;2086:139-150 Authors: Mizukami A, Swiech K Abstract Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the immunotherapy field with high rate complete responses especially for hematological diseases. Despite the diversity of tumor specific-antigens, the manufacturing process is consistent and involves multiple steps, including selection of T cells, activation, genetic modification, and in vitro expansion. Among these complex manufacturing phases, the choice of culture system to generate a high number of functional cells needs to be evaluated and optimized. Flasks, bags, and rocking motion bioreactor are the most used platforms for CAR-T cell expansion in the current clinical trials but are far from being standardized. New processing options are available and a systematic effort seeking automation, standardization and the increase of production scale, would certainly help to bring the costs down and ultimately democratize this personalized therapy. In this review, we describe different cell expansion platforms available as well as the quality control requirements for clinical-grade production. PMID: 31707673 [PubMed - in process]
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research

Related Links:

CONCLUSIONS: PD-L1 inhibitors lead to immune mediated thyroiditis, the most frequent endocrine IRAE. In most cases, management is supportive without requiring steroids or discontinuation of immunotherapy. Diffusely increased thyroid 18FDG uptake on PET scan may predict the occurrence of thyroiditis, whereas TPO antibodies may help identify its severity. Thyroiditis may be a biomarker for anti-tumor immune response, highlighting the need to further characterize its underlying mechanism. PMID: 31813343 [PubMed - as supplied by publisher]
Source: Thyroid : official journal of the American Thyroid Association - Category: Endocrinology Tags: Thyroid Source Type: research
We describe 2 children from unrelated families who presented with hypotonia, ptosis and fatigability in early infancy with anti-AChR antibodies detected via ELISA on 2 separate occasions in the sera. Both were treated as refractory autoimmune MG due to poor clinical response to acetylcholinesterase inhibitor and immunotherapy. In view of the atypical clinical features, genetic studies of CMS were performed and both were confirmed to have novel pathogenic mutations in the COLQ gene. To the best of our knowledge, the presence of anti-AChR antibody in COLQ-related CMS has never been reported in the literature. The clinical pr...
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
In conclusion, polymeric nanomicelles provide a flexible and safe method for gene delivery to T lymphocytes. PMID: 31814915 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Authors: Zhang JJ, Zhang QS, Li ZQ, Zhou JW, Du J Abstract Programmed cell death ligand 1 (PD-L1) is a key suppressor of the cytotoxic immune response. In colorectal carcinoma (CRC), PD-L1 expression results in immune escape and poor prognosis. Extensive researches suggested that metformin had a potential efficacy of enhancing anti-tumor immune response in different types of cancer. However, the detail mechanisms underlying the efficacy in CRC are unclear. Here, we showed that metformin decreases PD-L1 and YAP1 expression in vitro and in vivo. After silencing or inhibiting YAP1 expression by Verteporfin (VP), the i...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Blinatumomab is superior to standard chemotherapy for children and young adults with high- or intermediate-risk B-cell acute lymphoblastic leukemia that has relapsed.
Source: National Institutes of Health (NIH) News Releases - Category: American Health Source Type: news
Conclusion.Detection of CDK12‐LOF genomic alterations and their association with FTDs in a diverse spectrum of malignancies suggests that immunotherapy approaches targeting FINAs derived from CDK12‐associated FTDs may be a broadly applicable strategy that could be explored across cancer types in a tumor‐agnostic manner.Implications for Practice.CDK12 inactivation in ovarian and prostate cancer results in the generation of focal tandem duplications, which can cause fusion‐induced neoantigens. In prostate cancer, CDK12 alterations have demonstrated promise as a potential predictive biomarker for response to immune ch...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Cancer Diagnostics and Molecular Pathology Source Type: research
We present a case of a 58-year-old female with anti-PD-1 immunotherapy-related small bowel perforation. The patient was on long-term therapy with nivolumab for metastatic non-small cell lung cancer. She presented to the emergency department with acute abdominal pain, in which the CT revealed a short segment of dilated distal ileum proximal to a very short segment of bowel with mural thickening and a perforation near the transition point. The patient underwent subsequent laparotomy, which confirmed the CT findings and revealed a short-segment of friable and dilated loop of distal ileum proximal to a stricture and a small pe...
Source: Emergency Radiology - Category: Emergency Medicine Source Type: research
Advanced non-small cell lung cancer (NSCLC) leads to a high death rate in patients and is a major threat to human health. NSCLC induces an immune suppressive microenvironment and escapes from immune surveillance in vivo. At present, the molecular mechanisms of NSCLC immunopathogenesis and the immune suppressive microenvironment induced by NSCLC have not been fully elucidated. Here, we focus on the effect of NSCLC cells on the development and differentiation of human CD1c+ conventional dendritic cell (DC) subsets mediated by CD205 and CD103. The peripheral blood mononuclear cells (PBMCs) were isolated from NSCLC patients an...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
The vast majority of cancer-related deaths are due to metastasis, a process that requires evasion of the host immune system. In addition, a significant percentage of cancer patients do not benefit from our current immunotherapy arsenal due to either primary or secondary immunotherapy resistance. Importantly, select subsets of dendritic cells (DCs) have been shown to be indispensable for generating responses to checkpoint inhibitor immunotherapy. These observations are consistent with the critical role of DCs in antigen cross-presentation and the generation of effective anti-tumor immunity. Therefore, the evolution of effic...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractThe treatment landscape for locally advanced or metastatic urothelial carcinoma has broadened significantly over recent years. New therapeutic options include immunotherapy with checkpoint inhibitors and targeted therapy with erdafitinib. Despite these advances, gaps remain in the selection and sequencing of optimal therapies. Treatment decisions are often influenced by several patient-specific factors such as tolerability and biomarker expression. Following progression while receiving front- and second-line therapies, there is no widely accepted standard of care for patients. Enrollment into a clinical trial is re...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
More News: Clinical Trials | Genetics | Hematology | Immunotherapy | Molecular Biology