• Researchers have found that a new treatment approach combining low-dose bortezomib (a chemotherapy drug) with specially engineered immune cells called BATs can help fight multiple myeloma, a type of blood cancer that is hard to cure and often returns after treatment. The drug increases a protein called PD-L1 on cancer cells, which the BATs target to activate the body’s
T cells to attack the cancer more effectively. Tests showed that this combination boosted the immune system’s ability to kill multiple myeloma cells, even in cases where the cancer is resistant to bortezomib alone, offering hope for better treatments in the future.

• Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by frequent relapse due to acquired treatment resistance, underscoring the need for innovative therapies, particularly for relapsed cases. This study explores the effects of low-dose bortezomib (BTZ) on programmed death ligand 1 (PD-L1) expression in MM cell lines and its potential to enhance T cell-mediated anti-tumor responses. Utilizing this PD-L1 upregulation, we employed bispecific αPD-L1 ×αCD3 T cell engagerarmed T cells (BATs) to block PD-L1 signaling and activate T cells. Flow cytometry confirmed that BATs selectively bound CD3 on T cells and PD-L1 on cancer cells, inducing T cell activation and proliferation without directly affecting cancer cell viability. BATs’ cytotoxic activity was evaluated in MM cell lines with or without BTZ-induced PD-L1 expression. While KMS-12-PE cells showed no significant response, BATs significantly increased cell death in L363 cells, with further enhancement by BTZ. In RPMI-8226 cells, BATs demonstrated robust cytotoxicity, further amplified by BTZ. These results suggest that BATs, particularly in combination with BTZ, represent a promising strategy for treating MM, including bortezomib-resistant cases.