A Personalized Cancer Nanovaccine that Enhances T-Cell Responses and Efficacy Through Dual Interactions with Dendritic Cells and T Cells

Abstract

Conventional approaches to developing therapeutic cancer vaccines that primarily activate tumor-specific T cells via dendritic cells (DCs) often demonstrate limited efficacy due to the suboptimal activation of these T cells. To address this limitation, here a therapeutic cancer nanovaccine is developed that enhances T cell responses by interacting with both DCs and T cells. The nanovaccine is based on a cancer cell membrane nanoparticle (CCM-MPLA) that utilizes monophosphoryl lipid A (MPLA) as an adjuvant. To allow direct interaction between the nanovaccine and tumor-specific T cells, anti-CD28 antibodies (aCD28) are conjugated onto CCM-MPLA, resulting in CCM-MPLA-aCD28. This nanovaccine activates tumor-specific CD8+ T cells in both the presence and absence of DCs. Compared with nanovaccines that interact with either DCs (CCM-MPLA) or T cells (CCM-aCD28), CCM-MPLA-aCD28 induces more potent responses of tumor-specific CD8+ T cells and exhibits a higher antitumor efficacy in tumor-bearing mice. No differences in T cell activation efficiency and therapeutic efficacy are observed between CCM-MPLA and CCM-aCD28. This approach may lead to the development of effective personalized therapeutic cancer vaccines prepared from autologous cancer cells. A nanovaccine comprising cancer cell membrane, monophosphoryl lipid A, and anti-CD28 antibodies (named CCM-MPLA-aCD28) activates tumor-specific CD8+ T cells by interacting with both dendritic cells (DCs) and naive T cells. CCM-MPLA-aCD28 exhibits higher efficacy in tumor-specific T cell activation and tumor inhibition than nanovaccines that interact with either DCs (CCM-MPLA) or naive T cells (CCM-aCD28).image