ACT001 inhibits the proliferation of tumor cells and improves immune function in multiple myeloma.

Abstract Background ACT001 has strong anti-tumour and immune checkpoint modulating properties. Due to the ability to cross the blood-brain barrier, it has been widely used in glioma research and subjected to international phase 2-3 clinical trials.The possible roles and mechanisms of ACT001 in haematological malignancies, especially multiple myeloma, have not yet been determined. Methods We first examined the effect of ACT001 on the apoptotic proliferation of myeloma cells and also verified the associated pathway proteins. Next, CD3+ T cells and NK cells from mononuclear cell of bone marrow of healthy individuals and myeloma patients were sorted and co-cultured with myeloma cell lines in vitro. Changes in immune cell function and activity in the co-culture system were detected by drug addition. Results ACT001 promotes multiple myeloma cell apoptosis through the STAT3/BcL2 pathway and inhibits multiple myeloma cell proliferative activity through the NF-κB pathway. At the same time, the introduction of ACT001 into the culture system increased the cytotoxicity of immune cells and enhanced the activation of antibodies on the surface of natural killer cells, resulting in more tumour cell death Conclusion In this study, we found that ACT001 inhibited the activity of myeloma cells while enhancing the immune function of myeloma patients, suggesting that ACT001 is a small molecule drug with great clinical promise.