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Biomaterial Scaffold to Culture T Cells for Immune Cell Therapy

January 16th, 2018 Conn Hastings Genetics, Materials, Oncology

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…

Via: Harvard Wyss Institute…

Conn Hastings

Conn Hastings received a PhD from the Royal College of Surgeons in Ireland for his work in drug delivery, investigating the potential of injectable hydrogels to deliver cells, drugs and nanoparticles in the treatment of cancer and cardiovascular diseases. After achieving his PhD and completing a year of postdoctoral research, Conn pursued a career in academic publishing, before becoming a full-time science writer and editor, combining his experience within the biomedical sciences with his passion for written communication.

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