Nature Communications | Chinese Medical Team Innovates CAR-T Therapy to Bring New Hope for AML Treatment

Nature Communications | Chinese Medical Team Innovates CAR-T Therapy to Bring New Hope for AML Treatment

AML

In the field of hematological malignancies, the treatment of acute myeloid leukemia (AML) has long been a challenge in the medical community. Particularly for relapsed or refractory patients, the limitations of traditional treatments have increased the urgent need for new therapies. With the advancements in immunotherapy technology, the continuous updating of CAR-T cell therapy has brought new possibilities for the treatment of AML.

Recently, a study titled “CAR-T Cells with C-JUN Overexpression in Acute Myeloid Leukemia: Preclinical Features and Phase I Trial” was published in the journal Nature Communications. This study comprehensively explores the potential optimization mechanisms of CAR-T therapy in AML and was jointly completed by doctors and professors from three top hospitals in China.

During an interview, the Chinese medical team stated that in designing this study, they focused on the major obstacles in CAR-T cell therapy for AML. Although CD33, a highly expressed target, has been extensively explored in multiple studies, safety and efficacy remain challenges. The study found that high expression of CD155 affects the ERK signaling pathway, thereby hindering the effective expansion of CD33. To address this challenge, the research team ultimately selected the overexpression of C-JUN to enhance the exhaustion resistance of CAR-T cells by screening ERK pathway genes. Preliminary results from the clinical trial showed that this overexpressed CD33 CAR-T cell exhibited significant advantages in antitumor function.

Despite the progress, the challenges in CAR-T therapy for AML treatment were also emphasized, including the balance between high efficacy and low toxicity, the expansion of CAR-T cells in myeloid leukemia cells, and the affinity of antibody binding. Subsequent research will focus more on addressing these key issues to enable more patients to benefit from CAR-T therapy.

The Chinese clinical trials revealed some key findings of CAR-T therapy, such as the effectiveness of the bridging transplant strategy and the remarkable efficacy of CD33 CAR-T cells derived from transplant donors. These studies not only provide new insights into the application of CAR-T therapy in AML but also offer references for the optimization of therapies targeting other antigens.

The Chinese medical team will continue to conduct in-depth research around the three core issues of toxicity, expansion, and antigen binding, aiming to overcome challenges and enable more patients to benefit from the breakthrough results of CAR-T cell therapy.

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