CAR T-cell Therapy for AML

Dear Colleagues,

Recent advances in the molecular profiling of acute myeloid leukemia (AML) has refined prognostic risk stratification, improved minimal residual disease monitoring and personalized treatment options with new precision drugs. Despite these substantial improvements, up to 70% of adults and 30% of children with AML still relapse after initial responses and do not survive beyond five years.

Chimeric antigen receptor (CAR) T cells have dramatically improved the outcome of patients with high-risk B cell malignancies, while their successful deployment for other malignancies such as AML remains an open challenge. So far, antigen selection is the most significant barrier restricting the therapeutic application of CAR T cells in AML. Novel CARs redirected against unexplored AML targets recently proved to be specific in preclinical models, while selective AML antigen combinations have been proposed for dual targeting strategies exploiting high-throughput approaches. However, differential expression between leukemic and normal hematopoietic cells should not be the only parameter to select targets for immunotherapy in a highly heterogeneous genotypic and phenotypic cancer as AML. Thus, AML targets should be ideally integral to leukemic functions, especially considering antigen loss or downregulation as a major mechanism of relapse after CAR-T cell therapy.

I hope that this Special Issue will contribute to the dissemination of original research and comprehensive reviews of the exploration of novel AML targets, mechanisms of CAR-T cell failure in AML and strategies to overcome these issues.

Dr. Vincenzo Maria Perriello
Guest Editor

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• chimeric antigen t cells
• acute myeloid leukemia
• immunotherapy
• adoptive cell therapy
• gene therapy
• T cell receptor (TCR)-based therapy
• leukemic stem cells
• leukemia target antigens
• tumor microenvironment