Scientists discover a new approach to rapidly expand T cells ex-vivo that can be useful for anti-cancer immunotherapeutic approaches.
The development of safe and effective T cell−based anti-cancer immunotherapies is continually developing and have led to some successes. This approach depends on the rapid ex vivo expansion of functional T cells. However, current methods to achieve this are met with a number of challenges that limit the ability to obtain sufficient T cells in less than the several weeks necessary to expand the cells.
Activation of T cells requires stimulation of T cell receptors, costimulation (by helper T cells, dendritic cells, and/or released cytokines), and the production of cytokines that promote T cell survival. Antigen-presenting cells (APCs) are key components of the immune system necessary for T cell activation. Given the limitations and known factors necessary for T cell activation and expansion, a group of scientists at Harvard's Wyss Institute developed a biomaterial that acts as a scaffold made of mesoporous silica rods coated with a supported lipid bilayer containing T cell−activating molecules.
This biomaterial, termed APC-mimetic scaffolds, were used to achieve expansion of human and mouse T cells. When primary human blood cells (specifically T cells) were cultured on the scaffold biomaterial, larger T cell clusters were possible when compared to culture with Dynabeads (the gold standard for CAR-T cell expansion). There was a 2 to 10 times greater T cell expansion with the biomaterial than with the use of Dynabeads. To determine the antigen-specificity of the scaffold material, the researchers used APC-mimetic scaffolds presenting Epstein–Barr virus (EBV)- associated peptides. Even when culturing heterogeneous human primary blood cells with the scaffolds, there was a rapid increase in EBV-peptide−specific cytotoxic T cells in the APC-mimetic−scaffold treated human primary blood cell cultures (60-fold expansion by day 7 of culture).
T cells expanded on the tested biomaterial were also found to maintain functionality. CD19-specific CAR-T cells expanded on the scaffolds or Dynabeads were compared by treating a lymphoma mouse model with the cells. The scaffold-expanded CAR-T cells had the same anti-tumor efficacy as those expanded on Dynabeads. The study results show that the tested biomaterial can mimic T cell activating cues that are present in vivo and can serve as a means to more rapidly expand functional T cells useful for anti-cancer immunotherapeutic approaches.
Fast-tracking T-cell therapies with immune-mimicking biomaterials: A new approach to amplify patient-specific T cells outside the body could increase the efficiency of cancer immunotherapies. (2018). ScienceDaily. Retrieved 23 February 2018, from https://www.sciencedaily.com/releases/2018/01/180115120555.htm