Immunofilaments Provide a Nanoscale Platform for In Vivo T Cell Expansion and Cancer Immunotherapy

Adoptive T cell therapy has successfully been implemented for the treatment of cancer. Nevertheless, the precarious ex vivo expansion of T cells by artificial antigen-presenting cells (aAPCs) remains cumbersome and can compromise T cell functionality, thereby limiting their therapeutic potential. Here, we propose a radically different approach aiming at direct expansion of T cells in vivo, thereby omitting the need for large-scale ex vivo T cell production. We engineered nanosized immunofilaments (IFs), consisting of a soluble semiflexible polyisocyanopeptide polymer backbone that presents peptide-loaded major histocompatibility complexes and co-stimulatory molecules in a multivalent fashion. We demonstrate that IFs readily activate and expand antigen-specific T cells in a manner highly similar to natural APCs, as evidenced by transcriptomic analyses of T cells. Upon intravenous injection, IFs reach lymphoid organs including spleen and lymph nodes and induce antigen-specific T cell responses in vivo. Moreover, IFs display remarkable anti-tumor efficacy resulting in inhibition of melanoma metastases formation and reduction of primary tumor growth in synergy with immune checkpoint blockade. In conclusion, nanosized IFs represent a powerful new type of aAPC that provide a modular platform for direct activation and expansion of antigen-specific T cells in vivo, which can greatly contribute to cancer immunotherapy. ### Competing Interest Statement C.F. is the chief scientific officer and co-founder of Simmunext biotherapeutics develops novel immunotherapies by mimicking immune cell function through its proprietary polymer platform technology. C.F. is an inventor on patent WO2012004369 (2012); C.F., R.H. and L.J.E. are inventors on patent WO2019154865 (2019); C.F., R.H. and M.V. are inventors on patent WO2020174041. The other authors declare no conflict of interest.