Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies

Area of Science:

• Immunology
• Materials Science
• Biotechnology

Background:

• Chimeric antigen receptor (CAR)-engineered T cells are crucial for cancer therapy.
• Current CAR T cell manufacturing lacks effective immunological synapse formation.
• This limitation hinders optimal T cell expansion and function.

Purpose of the Study:

• To develop a novel platform for improved CAR T cell manufacturing.
• To mimic in vivo immunological synapses for enhanced T cell activation.
• To increase CAR T cell proliferation, potency, and gene-engineering efficiency.

Main Methods:

• Development of a flexible graphene oxide antigen-presenting platform (GO-APP).
• Decoration of graphene oxide with anti-CD3 (αCD3) and anti-CD28 (αCD28) antibodies (GO-APP^3/28).
• In vitro assessment of T cell interactions with GO-APP^3/28, including proliferation, multifunctionality, and gene-engineering efficiency.

Main Results:

• GO-APP^3/28 successfully mimicked in vivo immunological synapses.
• Achieved remarkable T cell proliferation and preserved T cell multifunctionality and potency.
• Enhanced CAR gene-engineering efficiency by over fivefold compared to standard protocols.
• Stimulated autocrine interleukin-2 (IL-2) production, reducing reliance on external IL-2 supplementation.

Conclusions:

• The GO-APP^3/28 platform offers a superior method for CAR T cell manufacturing.
• This approach improves T cell expansion and function for cancer immunotherapy.
• It presents a potential strategy for IL-2 independent T cell culture.