Semi-flexible immunobrushes facilitate effective and selective expansion of antigen-specific T cells

Abstract

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.