The therapeutic effect of cancer vaccines is critically dependent on the anti-tumor immunity mediated by CD8+ T cells. However, due to insufficient T cell activation, the efficacy is limited. Inspired by the close interaction between cellular physiological state and immune regulatory function, we proposed the ASCENT platform, which integrates activated platelets and senescent tumor cells-produced nanovesicles with naturally presented antigens and co-stimulatory molecules, thereby achieving dual-pathway T cell activation. Specifically, senescent tumor cells promote antigen presentation by up-regulating major histocompatibility complex I (MHC-I) molecules, while activated platelets increase the surface expression of CD40L and OX40L, thereby enhancing immune activation. Therefore, without the need for genetic or chemical engineering, ASCENT can effectively stimulate CD8+ T cells through antigen self-presentation and dendritic cell-mediated antigen delivery, ultimately triggering a robust immune response. This non-engineered, physiologically regulated nanovaccine demonstrates broad-spectrum anti-tumor activity and induces long-lasting systemic immune memory, effectively inhibiting tumor recurrence and metastasis. In summary, the ASCENT nanovaccine provides a new perspective for rational vaccine design, emphasizing the importance of direct and indirect T cell activation in strengthening cancer immunotherapy.
This study was published in Advanced Materials under the title "Non-Engineered Physiologically Modulated Nanovesicles Augment Antitumor Immune Responses via Dual-Pathway T Cell Activation".
References: DOI: 10.1002/adma.73231