Researchers developed a new, biomaterials-based system that takes a soft approach to improving cell manufacturing and may bring new hope to cancer patients for T-cell therapy. The study findings were published in Advanced Biosystems.
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, chemical-based approaches.
A current bottleneck in the approaches and other Adoptive T-cell Therapies (ACTs) is the production of sufficient numbers of high-quality T cells. As a starting material, cells are isolated from the patient and then modified and grown outside the body in a bioreactor.
In addition to technical challenges faced inconsistent production of cells, T cells from patients undergoing treatment for cancer often show reduced function due to the disease, and are particularly difficult to grow.
The team has developed a new method for improving T-cell manufacture by focusing on the materials involved in this process. The team include immune engineering and smart biomaterial design and they used a polymer mesh to activate the T cells.
The report shows that this soft mesh material increases the number of functional cells that can be produced in a single step. In fact, the system provided nearly an order of magnitude more cells in a single process.
The team has been able to expand cells isolated from patients undergoing treatment for leukaemia. These cells are often very difficult to activate and expand, and this has been a barrier to using cellular immunotherapy for the people who need it.
In testing the effect of a softer material on T-cell production, the team was inspired by the field of mechanobiology. Researchers have known that other cell types can sense the mechanical stiffness of a material.
For example, the rigidity of a material used to culture stem cells can direct differentiation, with a softer material promoting the production of the neuron while a stiffer substrate encourages bone cell differentiation. This effect can be as strong as the chemicals normally used to direct differentiation. However, a similar effect was unexpected in T cells for activation.
This makes sense for cells normally involved in force-related activities, like muscle cells or fibroblasts that are involved in wound closure and healing. For the first time, the team explored the possibility for T cells, which are not associated with such functions.
The experiment discovered that T-cells can sense the mechanical rigidity of the materials commonly used in the laboratory. To turn this into a clinically useful system, the researchers created a microfiber-based platform.
Beyond simplifying the process of cell expansion and improving T-cells expansion, the team envision that the mesh platform will have applications beyond immunotherapy. They are refining their platform and exploring how T cells from cancer patients respond to their materials. It was exciting to see how these bioinspired matrices can direct cell function and be successfully used for T-cell therapy.