Researchers at the Harvard Wyss Institute have developed a biomaterial scaffold that mimics the actions of antigen-presenting cells (APCs) in stimulating T cell growth and survival. The scaffold allowed the researchers to significantly expand T cell numbers in a dish, compared with existing culture methods, and could bring T cell therapies, such as anti-cancer treatments, closer to clinical reality.
Anti-cancer T cell therapies involve culturing and sometimes modifying patient-specific T cells in a dish before administering them to a cancer patient, where they can attack and kill cancer cells. A major challenge with this technique lies in achieving sufficient T cell growth and survival in vitro to obtain a sufficient dose of reactive T cells. At present, it can take weeks of expensive culture time to grow enough cells.
Researchers at the Harvard Wyss Institute took inspiration from another immune cell type, the APC, which stimulates T cells to grow and survive during an immune response. The researchers designed a biomaterial scaffold that provides pro-survival and pro-growth biological cues to T cells, just like an APC in the body.
T cells isolated from donors can access and move through an antigen-presenting cell-mimetic scaffold to receive cues and multiply. Credit: Wyss Institute at Harvard University
The research team used mesoporous silica rods to build their scaffold. They loaded the rods with Interleukin-2, a protein produced by APCs that can enhance T cell survival, and coated them using a lipid layer, to mimic the APC cell membrane. The team then incorporated antibodies to stimulate the T cells into the scaffold lipid “membrane”.
“Our approach closely mimics how APCs present their stimulating cues to primary T cells on their outer membrane and how they release soluble factors that enhance the survival of the T cells,” said David Mooney, a researcher who led the study. “As a result, we achieve much faster and greater expansion. By varying the compositions of lipids, cues, and diffusible factors in the scaffolds, we engineered a very versatile and flexible platform that can be used to amplify specific T cell populations from blood samples.”
Using the scaffolds, the researchers were able to expand T cells from mice and humans much faster than existing culture techniques, and they confirmed that the expanded cells have clinical potential in a mouse lymphoma model.
Top image: The left pane shows a scanning electron micrograph (SEM) of a basic scaffold made of many tiny mesoporous silica rods (MSRs) before they are coated with a thin supported lipid bilayer (SLB) with the incorporated T cell-stimulating cues. In the right SEM image, T cells (in blue) bind to a section of a completed antigen-presenting cell-mimetic scaffold (in brown), where they are instructed to multiply and are kept alive for future use in T cell therapies. Credit: Wyss Institute at Harvard University
Study in Nature Biotechnology: Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells…
