Black phosphorus quantum dots conjugated with dual antibodies improve tumor infiltrating CD8 + T cell activation and cancer immunotherapy

Abstract

Abstract Tumor-infiltrating lymphocyte(TIL) therapy, an immunotherapy that uses CD8+T as the main killer cells isolated from the patient's tumor tissue to treat the patient's tumor, has shown efficacy in solid tumors. In the tumor microenvironment, effector CD8+T cells enter a state of impaired function known as T cell exhaustion. Therefore, how to improve their activity and rapid expansion in vitro is the key problem to be solved in TIL therapy. Combination immunotherapy has recently emerged as a potent cancer treatment strategy. And nanomaterials have shown great application value in the field of immunotherapy. We achieved optimal activation and amplification of CD8+T cells by combining organic nanomaterial black phosphorus quantum dots(BPQDs) with immune checkpoint inhibitory molecules PD-1 and LAG3. CD8+T cells enhanced cytotoxic function through a series of biomarkers (TNF-a and IFN-γ secretion) and targeted cell-killing measurements in vitro. It was related to the increase of CD8+T cells, and the increased function was more than the number of cells increased, indicating that the function of CD8+T cells was also enhanced. This work demonstrates a novel strategy for using organic nanotechnology to improve effective expansion and efficacy of tumor-infiltrating lymphocytes.