CELL INTELLIGENCE · 肿瘤细胞治疗研究

Dendritic cells (DC) demonstrate supporting function in the immune system, cross-presenting tumour associated antigens to T lymphocytes and inducing a cascade immune response, thereby playing a role as a cell vaccine to enhance CAR-T cell functions. The normal expression of Natural killer group 2 member D (NKG2D) on immune cells and the high expression of its ligands on cancer cells have spurred research on the development of second-generation CAR design, aiming to break free from the impasse in solid tumour treatment. However, the tumour microenvironment (TME) created by the immaturity of immune cells and the cleavage of ligands can impair immune cell functions. In this study, we used GM-CSF/IL-4 to stimulate murine bone marrow DCs to generate an immature DC complex, which would later undergo lentiviral infection to develop mature DCs as vaccine. Next, we designed ribonucleic acid export 1(RAE1)-armoured DC to boost NKG2D-CAR-T cell functions, such as tumour cytotoxicity, central memory phenotype shift, cell activation, cell proliferation and survival. BALB/c mice were received murine osteosarcoma cell K7M2/luc transplantation as orthotopic xenograft model, while combined treatment (DCs and T cells) and boost treatment (DC only) were arranged on Day 1 and Day 15. We conducted both in vitro assessment and in vivo evaluation to potentially mitigate the influence of a restricted TME caused by hypofunctional DCs and the competition for recognition from soluble NKG2D ligands. Our research results demonstrate an improvement over previous DC vaccine applications and show a promising future for CAR-T therapy in solid tumour treatment.