AML —is it time to drive a CAR(-T)?

SummaryThe treatment options for newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) have substantially improved over the last 5  years. However, even though novel targeted agents (e.g. venetoclax, IDH1/2 and novel FLT-3 inhibitors; cytosolic isocitrate dehydrogenase 1/2 and fms-like tyrosine kinase 3 inhibitor) and improved chemotherapeutics (e.g. CPX-351; liposomale Daunorubicin/Cytarabine) are entering clinics, physician s are still confronted with high relapse and treatment failure rates. Thus, novel new strategies are required to improve AML therapy. Application of genetically engineered T cells (i.e. chimeric antigen receptor T cells, CAR-T cells) has proven to be highly effective in B cell-derived neoplasia a nd early data suggest also a high potential in the treatment of AML. This short review highlights the current approaches but also limitations of CAR-T cell therapy in AML precluding their current routine clinical use. Among a plethora of problems to be overcome, a critical issue will be to find r elatively selective actionable targets in AML.
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research

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In spite of the recent approval of new promising targeted therapies, the clinical outcome of patients with acute myeloid leukemia (AML) remains suboptimal, prompting the search for additional and synergistic therapeutic rationales. It is increasingly evident that the bone marrow immune environment of AML patients is profoundly altered, contributing to the severity of the disease but also providing several windows of opportunity to prompt or rewire a proficient antitumor immune surveillance. In this Review, we present current evidence on immune defects in AML, discuss the challenges with selective targeting of AML cells, an...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Contributors : Ling Li ; Xin HeSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWe want to obtain FLT3-ITD gene signature. To do so, we transduced CB CD34+ cells with mock or FLT3-ITD vectors and performed RNA sequencing (RNA-Seq).Two Groups: Group1: CB CD34+ cells transduced with mock vector; Group2: CB CD34+ cells transduced with FLT3-ITD vector;
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Acute myeloid leukemia is a heterogeneous disease with a 5-year survival rate of 28.3%, and current treatment options constrained by dose-limiting toxicities. One of the key signaling pathways known to be frequently activated and dysregulated in AML is PI3K/AKT. Its dysregulation is associated with aggressive cell growth and drug resistance. We investigated the activity of Phenybutyl isoselenocyanate (ISC-4) in primary cells obtained from newly diagnosed AML patients, diverse AML cell lines, and normal cord blood cells. ISC-4 significantly inhibited survival and clonogenicity of primary human AML cells without affecting no...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Modern Pathology, Published online: 01 April 2020; doi:10.1038/s41379-020-0531-2Clinico-pathologic characteristics and outcomes of the World Health Organization (WHO) provisional entity de novo acute myeloid leukemia with mutated RUNX1
Source: Modern Pathology - Category: Pathology Authors: Source Type: research
A new combination of old drugs has shown'unexpectedly'higher response rates in patients with relapsed/refractory acute myeloid leukemia.Medscape Medical News
Source: Medscape Hematology-Oncology Headlines - Category: Cancer & Oncology Tags: Hematology-Oncology News Source Type: news
Schematics of the experimental protocol used to demonstrate the selective anti ‐tumor effect of the OSKM factors in vivo. Briefly, HSPCs from reprogrammable mice were isolated, infected in culture for 2 days with a retrovirus containing MLL‐AF9‐GFP and transplanted into sublethally irradiated mice. One week later the percentage of GFP+ cells in the bone marrow and bloo d was determined and animals treated with doxycycline (doxy) for 1 week to activate OSKM in the donor cells or left untreated (no doxy). The mice were then monitored for several months for the onset of leukemia and death. While untreated animals...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Commentary Source Type: research
Condition:   Cancer Intervention:   Drug: PARP Inhibitors Sponsor:   University Hospital, Caen Active, not recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Stem Cells and Development, Ahead of Print.
Source: Stem Cells and Development - Category: Stem Cells Authors: Source Type: research
AbstractThe aim of this work is to investigate the different expression patterns of B cell-specifics moloney murine Leukemia virus integration site-1 (BMI-1) and brain and acute leukemia, cytoplasmic (BAALC) genes, their prognostic and clinical significance in newly diagnosed cytogenetically heterogenous adult acute myeloid leukemia patients. BMI-1 and BAALC expression was detected in the bone marrow of patients using quantitative real-time reverse transcription polymerase chain reaction with cut off value set at 50th percentile for both genes. BMI-1 and BAALC overexpression was detected in 50% of cases which suggest their...
Source: Indian Journal of Hematology and Blood Transfusion - Category: Hematology Source Type: research
hüle R Abstract Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR + . The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The...
Source: Chembiochem - Category: Biochemistry Authors: Tags: Chembiochem Source Type: research
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