Adoptive T cell therapy
has successfully been implemented
for the
treatment of cancer. Nevertheless, 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. We propose a radically different approach aimed 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), with a soluble semiflexible polyisocyanopeptide backbone that
presents peptide-loaded major histocompatibility complexes and costimulatory
molecules multivalently. IFs readily activated and expanded antigen-specific
T cells like natural APCs, as evidenced by transcriptomic analyses
of T cells. Upon intravenous injection, IFs reach the spleen and lymph
nodes and induce antigen-specific T cell responses in vivo. Moreover,
IFs display strong antitumor efficacy resulting in inhibition of the
formation of melanoma metastases and reduction of primary tumor growth
in synergy with immune checkpoint blockade. In conclusion, nanosized
IFs represent a powerful modular platform for direct activation and
expansion of antigen-specific T cells in vivo, which can greatly contribute
to cancer immunotherapy.