Synthetic Scaffold Loaded With T Cells Shrinks Solid Tumors

Researchers in Seattle are now reporting success with a biopolymer synthetic scaffold loaded with cancer-fighting T cells and a mix of nutrients to potentially combat solid tumors.

A study published in The Journal of Clinical Investigation, investigators revealed that the scaffold loaded with T cells shrank tumors in mouse models of pancreatic cancer and melanoma more effectively than T cells that were delivered via injection.

“The key to our scaffold is that it’s not just a structure,” said senior study author Matthias Stephan, MD, PhD, who is in the Clinical Research Division at Fred Hutchinson Cancer Research Center in Seattle. “The components we’ve engineered into these scaffolds include an optimal mix of stimulating factors and other ingredients that allow the T cells to survive and proliferate and to maintain a sustained fight against cancerous cells.”

In the study, the researchers equipped the scaffold with chimeric antigen receptor (CAR T) cells. Therapies using CAR T cells have demonstrated positive results in patients with hematologic malignancies. However, that has not been the case with solid tumors for several reasons. Part of the problem is that solid tumors create an immunosuppressive microenvironment that inactivates T-cell responses and there is phenotypic diversity in solid tumors that eludes CAR T-cell targeting.

Stephan and his team hope they can overcome those obstacles. The sticky, sponge-like, dissolvable biopolymer scaffold consists of tiny pores and can be made into just about any size or shape. With collaborators at the Massachusetts Institute of Technology and University of Washington, the team developed implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors. 

These devices exposed high concentrations of immune cells for a substantial time period. Besides showing greater antitumor capabilities in immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, the researchers also demonstrated that the co-delivery of stimulator of interferon genes (STING) agonists may be able stimulate immune responses to eliminate tumor cells.

Researchers envision using genetic profiling of a patient’s tumor tissue to reveal the protein makeup of the tumor. A scaffold would be created from a mix of T cells and other ingredients designed to target the variety of tumor proteins in the patient’s particular tumor. The scaffold itself would dissolve after about a week, so it would not need to be removed in another surgical procedure.

Stephan said this scaffolding technology may be an option in the future as a form of palliative care for patients who don’t qualify for or don’t want surgery, but would benefit from shrinking their tumor.

Other uses include shrinking a large tumor so it can be more easily removed and inserting the scaffold postoperatively to mop up any remaining cancerous cells.