CELL INTELLIGENCE · 肿瘤细胞治疗研究

Current pancreatic cancer immunotherapy focused on alphabeta ( ) T cells, either through CD3-engaged bispecific antibodies or CAR-T. Despite their promise, dose-limited toxicity (DLT) remains a challenge in clinical practice. In light of these concerns, there is a growing interest in exploring alternative T cell types, natural killer T (NKT) cells and gammadelta ( ) T cells, that possess the capacity to lyse tumors while potentially offering a safer therapeutic profile with fewer side effects. These cells present a compelling alternative that warrants a comprehensive evaluation of their therapeutic potential and safety profile. This study employed a MSLN/CD3 bispecific antibody to compare the anti-tumor activity of NKT and T cells with peripheral blood mononuclear cells (PBMCs) as controls, both in vitro and in vivo . This study demonstrated that MSLN/CD3 BsAb effectively activated and recruited PBMCs, NKT and T. Furthermore, under the influence of MSLN/CD3 BsAb, T and NKT cells exhibited notably superior anti-tumor activity compared to PBMCs, both in vitro and in vivo , while demonstrating low cytokine release. T cells showed almost negligible toxic side effects. In addition, the systemic administration of NKT and T cells activators, -galactosylceramide ( -GalCer) and Zoledronate, could enhance the anti-tumor effect of MSLN/CD3 bsAb, with no apparent toxicity. NKT and T cells are promising synergistic therapeutic cell types that may overcome the limitations of CD3 bispecific antibodies in pancreatic tumor treatments, offering a new perspective for clinical applications in immunotherapy.