Cellular Immunotherapy for Acute Myeloid Leukemia: From Bench to Bedside
TL;DR
It is concluded that while cellular immunotherapies represent a transformative frontier in AML treatment, their broad application is currently constrained by target antigen heterogeneity, a complex tumor microenvironment, and significant toxicities.
Abstract
Acute myeloid leukemia is a clonal malignant disease that arises from hematopoietic stem cells and is characterized by high genetic heterogeneity. AML has a poor prognosis, with a low 5-year survival rate, and is typically treated with chemotherapy. The management of AML, particularly for cases that are relapsed or refractory to conventional chemotherapy and transplantation, remains a formidable clinical challenge. This comprehensive review systematically evaluates the current landscape of cellular immunotherapeutic strategies for AML. We focus on the mechanisms of action, recent clinical progress, and persistent challenges associated with a range of adoptive cell therapies. These include natural killer cell-based infusions, and engineered approaches such as chimeric antigen receptor-T, CAR-NK, and CAR-macrophage therapies. Furthermore, we examine the roles of tumor-infiltrating lymphocytes and cytokine-induced killer cells. Our analysis synthesizes evidence from preclinical studies and clinical trials to assess the potential of these modalities in inducing durable antileukemic responses. We conclude that while cellular immunotherapies represent a transformative frontier in AML treatment, their broad application is currently constrained by target antigen heterogeneity, a complex tumor microenvironment, and significant toxicities. Finally, this review discusses strategic innovations necessary to overcome these barriers, highlighting directions for future research aimed at enhancing the efficacy and safety of these promising treatments for AML patients.