Biopolymer codelivery of cells programmed to express chimeric antigen receptors (CAR T cells) and stimulator of IFN genes (STING) directly to the surface of solid tumors reduced tumor size and rates of metastasis more than systemic delivery, according to results of a study using mouse models of pancreatic cancer and melanoma.
STING agonists stimulate immune responses such that CAR T cells are more likely to recognize tumor, limiting the likelihood of escape variants developing.
Immunotherapy using CAR T cells has improved treatment of many hematologic malignancies, but CAR T cell therapy is frequently less effective in solid tumors. This effect is due, in part, to the solid tumor microenvironment being immunosuppressive and, therefore, inactivates T cell responses.
In addition, phenotypic variation characterizes solid tumors such that not all tumor cells express proteins that a given immunotherapy targets. This can allow escape variants that evade CAR T cell targeting to form.
This study first examined implanted biopolymer devices to administer CAR T cells directly to the surfaces of solid tumors in mouse models of pancreatic cancer and melanoma. Results indicated CAR T cells could move from the biopolymers to the tumors to decrease tumor size more than systemic delivery of CAR T cells.
Next, researchers used the biopolymer devices to simultaneously deliver CAR T cells and STING agonists. This co-delivery worked synergistically to stimulate CAR T cells to eradicate even more tumor cells and to limit the formation of escape variants.
Using the biopolymer alone with CAR T cells and together with CAR T cells and STING agonists improved the efficacy of CAR T cell therapy in these mouse models.
1. Smith TT, Moffett HF, Stephan SB, et al. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors [published online April 24, 2017]. J Clin Invest. doi: 10.1172/JCI87624