Direct In Vivo Activation of T Cells with Nanosized Immunofilaments Inhibits Tumor Growth and Metastasis

Adoptive T cell therapyhas successfully been implementedfor thetreatment of cancer. Nevertheless, ex vivo expansion of T cells byartificial antigen-presenting cells (aAPCs) remains cumbersome andcan compromise T cell functionality, thereby limiting their therapeuticpotential. We propose a radically different approach aimed at directexpansion of T cells in vivo, thereby omitting the need for large-scaleex vivo T cell production. We engineered nanosized immunofilaments(IFs), with a soluble semiflexible polyisocyanopeptide backbone thatpresents peptide-loaded major histocompatibility complexes and costimulatorymolecules multivalently. IFs readily activated and expanded antigen-specificT cells like natural APCs, as evidenced by transcriptomic analysesof T cells. Upon intravenous injection, IFs reach the spleen and lymphnodes and induce antigen-specific T cell responses in vivo. Moreover,IFs display strong antitumor efficacy resulting in inhibition of theformation of melanoma metastases and reduction of primary tumor growthin synergy with immune checkpoint blockade. In conclusion, nanosizedIFs represent a powerful modular platform for direct activation andexpansion of antigen-specific T cells in vivo, which can greatly contributeto cancer immunotherapy.