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.