scholarly journals Acute myeloid leukemia chimeric antigen receptor T-cell immunotherapy: how far up the road have we traveled?

2018 ◽  
Vol 9 (6) ◽  
pp. 135-148 ◽  
Author(s):  
Sarah K Tasian
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Antigen Receptor ◽  
Successful Implementation ◽  
Car T Cell ◽  
Car T ◽  
Acute Myeloid

Chemotherapy resistance and relapse remain significant sources of mortality for children and adults with acute myeloid leukemia (AML). Further intensification of conventional cytotoxic chemotherapy is likely not feasible due to the severity of acute and long-term side effects upon normal tissues commonly induced by these drugs. Successful development and implementation of new precision medicine treatment approaches for patients with AML, which may improve leukemia remission and diminish toxicity, is thus a major priority. Tumor antigen-redirected chimeric antigen receptor (CAR) T-cell immunotherapies have induced remarkable responses in patients with relapsed or chemorefractory B-lymphoblastic leukemia, and similar strategies are now under early clinical study in adults with relapsed/refractory AML. However, potential on target/off tumor toxicity of AML CAR T-cell immunotherapies, notably aplasia of normal myeloid cells, may limit broader implementation of such approaches. Careful selection of optimal target antigens, consideration of toxicity mitigation strategies, and development of methodologies to circumvent potential CAR T-cell resistance are essential for successful implementation of cellular immunotherapies for patients with high-risk AML.

scholarly journals Chimeric antigen receptor T cell therapies for acute myeloid leukemia

2020 ◽  
Vol 14 (6) ◽  
pp. 701-710
Author(s):  
Bin Gu ◽  
Jianhong Chu ◽  
Depei Wu
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Antigen Receptor ◽  
Target Antigen ◽  
Hematopoietic Stem ◽  
Car T ◽  
Acute Myeloid

AbstractChimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.

scholarly journals Chimeric Antigen Receptor (CAR) T Cell Therapy in Acute Myeloid Leukemia (AML)

2019 ◽  
Vol 8 (2) ◽  
pp. 200 ◽  
Author(s):  
Susanne Hofmann ◽  
Maria-Luisa Schubert ◽  
Lei Wang ◽  
Bailin He ◽  
Brigitte Neuber ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Acute Myeloid

Despite high response rates after initial chemotherapy in patients with acute myeloid leukemia (AML), relapses occur frequently, resulting in a five-year-survival by <30% of the patients. Hitherto, allogeneic hemotopoietic stem cell transplantation (allo-HSCT) is the best curative treatment option in intermediate and high risk AML. It is the proof-of-concept for T cell-based immunotherapies in AML based on the graft-versus-leukemia (GvL)-effect, but it also bears the risk of graft-versus-host disease. CD19-targeting therapies employing chimeric antigen receptor (CAR) T cells are a breakthrough in cancer therapy. A similar approach for myeloid malignancies is highly desirable. This article gives an overview on the state-of-the art of preclinical and clinical studies on suitable target antigens for CAR T cell therapy in AML patients.

scholarly journals Driving CAR T Stem Cell Targeting in Acute Myeloid Leukemia: The Roads to Success

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2816
Author(s):  
Ilaria M. Michelozzi ◽  
Efstratios Kirtsios ◽  
Alice Giustacchini
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Overall Survival ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T ◽  
Acute Myeloid

Current treatment outcome for acute myeloid leukemia (AML) patients is unsatisfactory and characterized by high rates of relapse and poor overall survival. Increasing evidence points to a crucial role of leukemic stem cells (LSC) and the bone marrow (BM) leukemic niche, in which they reside, in AML evolution and chemoresistance. Thus, future strategies aiming at improving AML therapeutic protocols are likely to be directed against LSC and their niche. Chimeric antigen receptor (CAR) T-cells have been extremely successful in the treatment of relapsed/refractory acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma and comparable results in AML are highly desirable. At present, we are at the dawn of CAR T-cell application in AML, with several preclinical studies and few early phase clinical trials. However, the lack of leukemia-specific targets and the genetic and phenotypic heterogeneity of the disease combined with the leukemia-induced remodeling of the BM microenvironment are limiting CAR T-cell exploitation in AML. Here, we reviewed AML-LSC and AML-BM niche features in the context of their therapeutic targeting using CAR T-cells. We summarized recent progress in CAR T-cell application to the treatment of AML, and we discussed the remaining therapeutic challenges and promising novel strategies to overcome them.

Chimeric antigen receptor T-cell therapy in the treatment of acute myeloid leukemia: Possible challenges

2021 ◽  
Vol 1 (2) ◽  
pp. 86
Author(s):  
TarunKumar Suvvari ◽  
RahulJagdishchandra Mittal ◽  
KanishkK Adhit ◽  
NagaPraneeth Vakkalagadda ◽  
Divya BalaA. M R. Salibindla
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Antigen Receptor ◽  
T Cell Therapy ◽  
Acute Myeloid

scholarly journals PS974 MODELING NKG2D-BASED CAR-T CELL THERAPY IN ANIMALS WITH ACUTE MYELOID LEUKEMIA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 439
Author(s):  
M. Fontaine ◽  
E. Breman ◽  
B. Demoulin ◽  
S. Bornschein ◽  
J. Bolsée ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
Myeloid Leukemia ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Acute Myeloid

scholarly journals 716. Durable Acute Myeloid Leukemia Remission Without Myeloablation in an Innovative Xenotolerant Mouse Model of CD44v6 CAR-T Cell Immunotherapy

2015 ◽  
Vol 23 ◽  
pp. S286
Author(s):  
Margherita Norelli ◽  
Monica Casucci ◽  
Barbara Camisa ◽  
Laura Falcone ◽  
Aurore Saudemont ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Mouse Model ◽  
Myeloid Leukemia ◽  
Car T Cell ◽  
Cell Immunotherapy ◽  
Car T ◽  
T Cell Immunotherapy ◽  
Acute Myeloid
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