Stimulation of CD8 T cells with membrane vesicles prepared from antigen presenting cells

Abstract

Immunotherapy has emerged as a promising tool to treat diseases via enhancing or suppressing immune responses of T cells. For infectious diseases and cancer, inducing expansion of antigen–specific CD8 T cells has proved effective in preclinical and clinical studies for eliminating infected or malignant cells. In this thesis a subcellular vaccine prepared by sonication of disrupted mature dendritic cells (DCs) followed by loading with specific peptides was developed and used to stimulate naïve CD8 T cells. To achieve this, a new culture method was developed to prepare large numbers of mature DCs from mouse bone marrow (BM). Cell disruption and sonication of these BMDCs yielded membrane vesicle nano-particles that were immunogenic for CD8 T cells both in vitro and in vivo. Notably, the in vivo immunogenicity of the vesicles was considerably increased when co-delivered with anti-CD9 antibodies and CpG oligodeoxynucleotides, especially when given in multiple injections. Preliminary experiments demonstrated the potential of membrane vesicles for cancer immunotherapy in murine models.