Acute myeloid leukemia chimeric antigen receptor T-cell immunotherapy: how far up the road have we traveled?
Sarah K TasianPublished in: Therapeutic advances in hematology (2018)
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.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- primary care
- oxidative stress
- healthcare
- quality improvement
- drug induced
- induced apoptosis
- locally advanced
- gene expression
- squamous cell carcinoma
- liver failure
- climate change
- young adults
- cardiovascular disease
- acute lymphoblastic leukemia
- clinical trial
- rheumatoid arthritis
- risk assessment
- bone marrow
- signaling pathway
- endothelial cells
- high glucose
- systemic lupus erythematosus
- respiratory failure
- replacement therapy
- chemotherapy induced
- acute respiratory distress syndrome