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CAR-T and CAR-NK cell therapies in AML: breaking barriers and charting the future
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CAR-T and CAR-NK cell therapies in AML: breaking barriers and charting the future
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Journal Article
CAR-T and CAR-NK cell therapies in AML: breaking barriers and charting the future
2025
Overview
Acute myeloid leukemia (AML), characterized by aggressive relapse and dismal survival, remains a formidable challenge despite conventional therapies. Chimeric antigen receptor (CAR)-engineered T and natural killer (NK) cells have emerged as groundbreaking immunotherapies, offering targeted eradication of leukemic stem cells (LSCs) and resistant blasts. CAR-T cells, leveraging antigens like CD123 and CD33, demonstrate early clinical success, with complete remission rates up to 66% in refractory/relapsed (R/R) AML. CAR-NK cells complement this approach through inherent tumor surveillance, reduced toxicity, and \"off-the-shelf\" feasibility. However, barriers such as antigen escape, heterogeneous immunosuppressive microenvironments (including intratumoral microbiota variations), and on-target/off-tumor toxicity persist, limiting durable responses. Innovations in dual-targeting CARs, cytokine-armored constructs, and CRISPR-edited universal cells aim to overcome these hurdles. Emerging strategies integrating checkpoint inhibitors, metabolic modulators, and AI-driven antigen selection promise to enhance efficacy and safety. This review synthesizes the evolving landscape of CAR-T/NK therapies, critically analyzing preclinical breakthroughs, clinical trial outcomes, and persisting challenges. By addressing manufacturing scalability, cost barriers, and long-term safety, cellular immunotherapy holds transformative potential to redefine AML management. As the field advances, interdisciplinary collaboration and biomarker-guided personalization will be pivotal in translating laboratory innovations into life-saving therapies for AML patients.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Animals
/ Antigens
/ Biomedical and Life Sciences
/ Cell
/ CRISPR
/ Humans
/ Immune checkpoint inhibitors
/ Immunotherapy, Adoptive - methods
/ Immunotherapy, Adoptive - trends
/ Killer Cells, Natural - immunology
/ Kinases
/ Leukemia
/ Leukemia, Myeloid, Acute - immunology
/ Leukemia, Myeloid, Acute - therapy
/ Patients
/ Receptors, Chimeric Antigen - immunology
/ Receptors, Chimeric Antigen - metabolism
/ Review
/ Success
/ Testing
/ Toxicity
/ Tumors
