In this study, the researchers focused on generating specialized immune cells called dendritic cells (DCs) that can activate MSLN-specific T cells. They utilized a lentiviral vector to create self-differentiated myeloid-derived antigen-presenting cells, termed MSLN-SmartDC, which efficiently recognize tumor cells expressing MSLN.

The researchers found that high levels of MSLN were present in approximately 57% of TNBC cases, highlighting its relevance as a target for therapy. Moreover, MSLN-SmartDC exhibited similar characteristics to DCs generated using traditional methods, but with the added benefit of enhanced maturation and function when a toll-like receptor 4 ligand called 40s ribosomal protein subunit 3 (RPS3) was introduced. This enhancement resulted in increased expression of immune-activating molecules and improved secretion of immune-stimulating cytokines.

Importantly, the MSLN-specific T cells activated by both MSLN-SmartDC and RPS3-MSLN-SmartDC demonstrated a remarkable ability to selectively target and kill TNBC cells expressing MSLN. They exhibited potent cytotoxic activity against TNBC cells in both two-dimensional and three-dimensional culture systems.

These findings provide strong evidence for the efficacy of MSLN-SmartDC in activating MSLN-specific T cell responses against TNBC. Additionally, the use of RPS3 further enhanced the cytolytic activity of these T cells, offering a potential alternative treatment approach for patients with TNBC.

This breakthrough brings renewed hope for individuals battling TNBC and paves the way for future research and development of immunotherapies targeting MSLN, ultimately aiming to improve outcomes for patients with this aggressive form of breast cancer.