In Vitro-Transcribed (IVT)-mRNA CAR Therapy Development.

In Vitro-Transcribed (IVT)-mRNA CAR Therapy Development. Methods Mol Biol. 2020;2086:87-117 Authors: Androulla MN, Lefkothea PC Abstract Chimeric antigen receptor (CAR) cancer immunotherapy uses autologous immune system's cells, genetically modified, to reinforce the immune system against cancer cells. Genetic modification is usually mediated via viral transfection, despite the risk of insertional oncogenesis and off target side effects. In vitro-transcribed (IVT)-mRNA-mediated transfection could contribute to a much safer CAR therapy, since IVT-mRNA leaves no ultimate genetic residue in recipient cells. In this chapter, the IVT-mRNA generation procedure is described, from the selection of the target of the CAR T-cells, the cloning of the template for the in vitro transcription and the development of several chemical modifications for optimizing the structure and thus the stability of the produced CAR IVT-mRNA molecules. Among various transfection methods to efficiently express the CAR molecule on T-cells' surface, the electroporation and the cationic-lipid mediated transfection of the CAR IVT-mRNAs are described. PMID: 31707670 [PubMed - in process]
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research

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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
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
(NIH/National Cancer Institute) New findings from a clinical trial show that treatment with the immunotherapy drug blinatumomab is superior to standard chemotherapy for children and young adults with high- or intermediate-risk B-cell acute lymphoblastic leukemia (B-ALL) that has relapsed. Those treated with blinatumomab had longer survival, experienced fewer severe side effects, had a higher rate of undetectable residual disease, and were more likely to proceed to a stem cell transplant.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology 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
AbstractThe poly-(ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib, have recently been approved for use in patients with metastatic breast cancer (BC) and germline BRCA 1 or 2 mutations due to improved progression-free survival compared to chemotherapy. An increasing number of clinical trials are evaluating the role of PARP inhibitors (PARPi) in BC, alone and in combination with other therapies (including immunotherapy), as well as in earlier stages of the disease. This review describes the unique mechanism of action of these drugs and puts into clinical context the results of pivotal clinical trials. We a...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
Conclusion.CSYS proves to be clinically applicable and useful in disclosing genomic alterations relevant to cancer target therapies and revealing biomarkers for immune checkpoint inhibitors.Implications for Practice.The study describes a specially designed sequencing panel assay to detect genomic alterations and features of 450 cancer genes, including its overall workflow and rigorous clinical and analytical validations. The distribution of pan‐cancer tumor mutational burden, microsatellite instability, gene rearrangement, and long insertion and deletion mutations was assessed for the first time by this assay in a broad ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Cancer Diagnostics and Molecular Pathology Source Type: research
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