Search

Adoptive T cell therapy (ACT) has achieved remarkable results in the treatment of cancer. Tumor‐antigen specific T cells are the main players in the clearance of cancerous cells, but generating large numbers is a major hurdle in clinical practice. One shortcoming of current expansion procedures is that the artificial presentation of T cell activating signals on rigid surfaces do not recapitulate the physiological presentation on a fluidic membrane. To address this, semi‐flexible poly(isocyanopeptide) (PIC) immunofilaments (IFs) are generated coated on micro‐sized magnetic beads (immunobrushes (IB)). IBs are functionalized with peptide‐loaded major histocompatibility complexes (pMHC, signal 1) and agonistic anti‐CD28 antibodies (αCD28, signal 2) to effectively expand and enrich antigen‐specific T cells. As a direct result of the immunobrush design, strong T cell activation and excellent tumor cell killing capacities are found. More importantly, high selectivity is demonstrated by strong expansion and enrichment of antigen‐specific T cells in a pool of non‐specific cells (93‐fold enrichment of antigen specific T cells in 7 days). The modular character of the immunobrush‐based strategy makes it a great platform for highly effective ACT‐based therapies. [ABSTRACT FROM AUTHOR]

The invention of nanosized biomaterials has paved the way for novel therapeutics that can manipulate cells on a nanoscale. Nanosized immunofilaments (IFs) are synthetic filamentous polymers consisting out of polyisocyanopeptides, which have been recently established as a powerful platform to activate specific immune cells in vivo such that they raise an antitumor immune response. However, toxicological effects or immunogenicity toward the IFs have not yet been investigated. In this study, we evaluated potential toxic or immunogenic effects in C57BL/6 mice upon intravenous or subcutaneous injection of nonfunctionalized IFs or immunostimulatory IFs over 30 days. We here present a detailed analysis of the gross pathology, hematological parameters, blood biochemistry, histology, and antibody-response against the IF backbone. Our results demonstrate that IFs do not induce severe acute or chronic toxicity in mice. After 30 days, we only found elevated IgG-titers in intravenously injected but not subcutaneously injected mice. In summary, we demonstrate that IFs can be administered into a living organism without adverse side effects, thereby establishing the safety of IFs as a therapeutic intervention., Competing Interests: The authors declare the following competing financial interest(s): 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., and R.H. are inventors on patent WO2019154865 (2019); C.F. and R.H. are inventors on patent WO2020174041. The other authors declare no conflict of interest., (© 2024 The Authors. Published by American Chemical Society.)