Donor-receptor coordination mediated multiple antigens capture and transport for augmented cancer immunotherapy

Abstract

The activation of tumor antigen-specific immune responses is critical for the success of tumor immunotherapy and the advancement of antitumor therapies. However, the limited availability of antigens derived from immunogenic cell death significantly impedes antitumor immunity. To optimize the utilization of the resulting antigens and enhance the tumor-specific immune response, we herein present a strategy that captures antigens in situ within a polymeric depot, facilitated by donor-receptor coordination interactions. An amphiphilic cationic copolymer containing pendant phenylboronic acid (PP) as an electron acceptor unit was synthesized to facilitate various forces with multiple antigens, thereby generating nanovaccines in situ. As the most potent antigen are cell membrane, phenylboronic acid can specifically interact with sialylated epitopes overexpressed on the tumor cell membrane through the formation of donor-receptor coordination. For antigen proteins, the PP could bind with antigens by hydrophobic or electrostatic interaction, thereby facilitating their capture and delivery into the cytosol of antigen-presenting cells (APCs) and activating tumor-specific T cells. This platform could be adapted for various antigens, including antigen protein, tumor lysate and tumor cell membrane, with electron-donating groups, providing a straightforward and robust strategy to enable nanovaccines with enhanced antigen capture capabilities, ultimately improving cancer immunotherapy.