The Clinical Study of CD19 UCAR-T Cells in Patients With B-cell Acute Lymphoblastic Leukemia (B-ALL)

Conditions:   B-cell Acute Lymphoblastic Leukemia (B-ALL);   Safety and Efficacy of CD19 UCAR-T Cells Intervention:   Biological: CD19 UCARTcells Sponsor:   Shanghai Longyao Biotechnology Inc., Ltd. Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials

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Authors: Wrona E, Jakubowska J, Pawlik B, Pastorczak A, Madzio J, Lejman M, Sędek Ł, Kowalczyk J, Szczepański T, Młynarski W Abstract Resistance to L-asparaginase (L-asp) is a major contributor to poor treatment outcomes of several subtypes of childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL). Asparagine synthetase (ASNS), legumain (LGMN) and cathepsin B (CTSB) serve a key role in L-asp resistance. The association between genetic subtypes of BCP-ALL and the expression of ASNS, LGMN and CTSB may elucidate the mechanisms of treatment failure. Bone marrow samples of 52 children newly diagnosed with...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Fielding AK Abstract The understanding and treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia have changed rapidly in the past 10 years. The outcome is equally as good as for Ph- disease, and with targeted tyrosine kinase inhibitor therapies in addition to chemotherapy, the novel immunotherapy approaches, and the extension of allogeneic hematopoietic stem cell transplant (allo-HCT) to older individuals, there is the potential to exceed this outcome. There is particular interest in reducing chemotherapy exposure and considering for whom allo-HCT can be avoided. However, the pat...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Muffly L, Curran E Abstract Observational findings demonstrating improved survival for younger adults following pediatric, as opposed to adult, acute lymphoblastic leukemia (ALL) regimens have been translated into international, prospective multicenter clinical trials testing the pediatric regimen in young adult ALL. The results of these studies confirm the feasibility of delivering the pediatric regimen in the adult oncology setting and establish the superiority of this approach relative to historical adult cooperative group regimen results. Specific toxicities, including thrombosis, hepatotoxicity, and o...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Schultz L, Gardner R Abstract Immunotherapies have been successfully developed for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) with FDA approval of blinatumomab, inotuzumab, and tisagenlecleucel for relapsed or refractory patients. These agents target either CD19 or CD22, which are both expressed on the surface of the leukemic blasts in the majority of patients. The use of these agents has greatly transformed the landscape of available treatment, and it has provided curative therapy in some patients. As the field has matured, we are learning that for most patients, the currently available ...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Advani AS, Copelan EA Abstract The landscape of acute lymphoblastic leukemia (ALL) has evolved significantly over the last few years. Identification of specific recurrent genetic alterations and of minimal residual disease (MRD) guides prognostic classification and management. Novel agents (eg, blinatumomab) have demonstrated encouraging results in relapsed/refractory (R/R) and MRD+ patients and are currently incorporated into upfront treatment in specific settings. Other new strategies include the incorporation of tyrosine kinase inhibitor-based therapy for patients with Philadelphia chromosome-like ALL a...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Winters A, Gore L Abstract Although almost 90% of children with acute lymphoblastic leukemia (ALL) and ∼60% of children with acute myeloid leukemia are cured with frontline therapy, relapse and chemotherapy resistance are significant challenges that contribute to morbidity and mortality. Even with long-term survival, the acute and chronic burdens of therapy are major issues for patients and families. Long-term side effects occur, including cardiac, endocrinologic, neurcognitive, orthopedic, and psychosocial problems, and healthy survivorship is frequently compromised. With goals of minimizing relapse a...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
This article reviews the current landscape of antibody-based and cellular immunotherapies under current clinical evaluation with an emphasis on active or soon-to-open phase 1 trials for children with relapsed/refractory AML. PMID: 31808843 [PubMed - in process]
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
CONCLUSION: NOTCH1 mutations were frequently detected in T All patients; however, these mutations did not affect the T ALL patient's outcome. The high prevalence of NOTCH1 mutations at diagnosis could be used for detection of minimal residual disease in T ALL. PMID: 31796666 [PubMed - as supplied by publisher]
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
ng Jung Salih Antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism by which antitumor antibodies mediate therapeutic efficacy. At present, we evaluate an Fc-optimized (amino acid substitutions S239D/I332E) FLT3 antibody termed 4G8-SDIEM (FLYSYN) in patients with acute myeloid leukemia (NCT02789254). Here we studied the possibility to induce NK cell ADCC against B-cell acute lymphoblastic leukemia (B-ALL) by Fc-optimized FLT3 antibody treatment. Flow cytometric analysis confirmed that FLT3 is widely expressed on B-ALL cell lines and leukemic cells of B-ALL patients. FLT3 expression did not correlat...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Tumor cells adapt to nutrient-limited environments by inducing gene expression that ensures adequate nutrients to sustain metabolic demands. For example, during amino acid limitations, ATF4 in the amino acid response induces expression of asparagine synthetase (ASNS), which provides for asparagine biosynthesis. Acute lymphoblastic leukemia (ALL) cells are sensitive to asparagine depletion, and administration of the asparagine depletion enzyme l-asparaginase is an important therapy option. ASNS expression can counterbalance l-asparaginase treatment by mitigating nutrient stress. Therefore, understanding the mechanisms regul...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
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