A novel HER-2-specific exosome-targeted T cell-based vaccine: immunotherapy of established lung metastasis in transgenic HLA-A2/HER-2 mice (155.37)

Abstract

Abstract CD4+ T cell vaccine has less been studied. In this study, we demonstrated that active CD4+ T (aT) cells with uptake of ovalbumin (OVA)-pulsed dendritic cell (DCova)-derived exosome (EXOova) express exosomal peptide/major histocompetibility complex (pMHC) I and costimulatory molecules. EXOova-uptaken (targeted) CD4+ aT (aTexo) cells can stimulate central memory CD8+ cytotoxic T lymphocyte (CTL) responses, more efficient in vivo antitumor immunity and long-term CD8+ T cell memory responses than DCova, and break the self immune tolerance in two transgenic mouse models leading to OVA- and neu-specific CTL-mediated diabetes and antitumor, respectively. We further elucidated that aTEXO’s stimulatory effect is mediated via its IL-2 secretion and acquired CD80 costimulation, and specifically targeted to CD8+ T cells in vivo via acquired pMHC I complexes. Therefore, EXO-targeted CD4+ T cell vaccine may represent a novel and highly effective vaccine strategy for inducing immune responses against not only tumors, but also other infectious diseases. Therefore, EXO-targeted CD4+ T cell vaccine may represent a novel effective vaccine strategy for therapeutic treatment of patients with early stage of HER-2-positive or trastuzumab-resistant HER-2-positive breast cancers, and for adjuvant treatment of patients with potential risk of metastasis after surgical treatment.