Self-differentiated Dendritic Cells Presenting NY-ESO-1 Prime Cytotoxic T Cells for the Treatment of Multiple Myeloma

Abstract

Background/Aim: Multiple myeloma (MM) remains incurable due to relapse and therapeutic resistance. This study evaluated the cancer-testis antigen NY-ESO-1 as a target for T-cell-based immunotherapy and assessed the potential of a self-differentiated monocyte-derived dendritic cell platform expressing NY-ESO-1 (SD-DC-NY) to activate T-lymphocytes against MM in vitro. Materials and Methods: NY-ESO-1 expression was assessed by immunohistochemistry (IHC) in 95 MM cases. A lentiviral tri-cistronic construct encoding GM-CSF, IL-4, and NY-ESO-1 was used to generate SD-DC-NY. Autologous T-lymphocytes were activated with SD-DC-NY and tested against NY-ESO-1-positive U266 and NY-ESO-1-negative JJN-3 cells. Cytotoxicity (annexin V/PI) and interferon-gamma (IFN-γ) secretion (ELISA) were measured. Statistical significance was set at α=0.05 using two-sided tests. Results: NY-ESO-1 was detected in 17.9% (17/95) of MM samples. SD-DC-NY showed DC maturation comparable to conventional cytokine-generated DCs. SD-DC-NY-activated T-lymphocytes induced higher apoptosis of U266 cells versus controls (p<0.0001) and secreted more IFN-γ (p< 0.05). Conclusion: SD-DC-NY effectively primes cytotoxic T-lymphocytes and enhances antitumor activity against NY-ESO-1positive MM cells, supporting NY-ESO-1 as an immunotherapeutic target and highlighting SD-DC-NY as a promising platform for MM immunotherapy.