UCLA researchers in the Department of Materials Science and Engineering have constructed a novel graphene oxide-based platform for robust T cell activation through artificial immune synapse formation.

BACKGROUND: T cells are a critical arm of the immune system with tremendous therapeutic value for immune disorders and cancer. However, modulation of T cells in a clinical context can be difficult due to low efficiency and off-target effects that lead to toxicity. Current methods for T cell activation and proliferation typically involve the addition of external interleuikin-2 (IL-2); however, these approaches typically result in suboptimal T cell activation. To improve upon the low efficiency of IL-2 activation alone, advancements have been made to utilize 2-D artificial antigen-presenting structure (AAPS) with anti-CD3 (αCD3) and anti-CD28 (αCD28). AAPS allows antibody interaction with T cells that closely mimics immune synapses between the antigen-presenting cells (APCs) and T cells in vivo. Commercial platforms such as Dynabeads (Invitrogen) have used this technology to stimulate T cells, but this method still requires external IL-2 with modest T cell activation rates. Thus, there is a pressing need for development of a more robust and efficient method of T cell stimulation.

INNOVATION: Researchers at UCLA have developed AAPS consisting of αCD3 and αCD28 anchored on graphene oxide for potent stimulation of T cell activation and proliferation. The state-of-the-art nanomaterial graphene is made up of few atomic layers thin profile which provides flexibility to conform to cell surfaces. This allows for large contact areas as well as high accessibility to the T cell receptors. Researchers have shown that the graphene oxide-based AAPS exhibits significantly higher efficiency than IL-2 treatment and Dynabeads in stimulating T cells. Due to graphene’s unique properties of biocompatibility and high physical and chemical stability, attached antibodies can be programmed in variety, density, and hierarchy. This provides a powerful GO-based systematic platform for T cell stimulation.

POTENTIAL APPLICATIONS:

• Platform technology for T cell activation and proliferation

ADVANTAGES:

• Increased magnitude efficiency rates of T cell stimulation compared to IL-2
• Flexibility of antibody attachments on graphene oxide

DEVELOPMENT-TO-DATE: Functional evaluation of AAPS in mouse model

Related Papers (from the inventors only): Zhu, E., Yu, J., Li, YR. et al. Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies. Nat. Nanotechnol. 19, 1914–1922 (2024). https://doi.org/10.1038/s41565-024-01781-4   

Keywords: Graphene, T cells, IL-2, biomimetics, antibodies, antigen presenting cell (APC), artificial antigen presenting structure, delivery systems, nanomaterials