Systemic enhancement of antitumour immunity by peritumourally implanted immunomodulatory macroporous scaffolds

A tumour microenvironment abundant in regulatory T (T-reg) cells aids solid tumours to evade clearance by effector T cells. Systemic strategies to suppress T-reg cells or to augment immunity can elicit autoimmune side effects, cytokine storms and other toxicities. Here we report the design, fabrication and therapeutic performance of a biodegradable macroporous scaffold, implanted peritumourally, that releases a small-molecule inhibitor of transforming growth factor beta to suppress T-reg cells, chemokines to attract effector T cells and antibodies to stimulate them. In two mouse models of aggressive tumours, the implant boosted the recruitment and activation of effector T cells into the tumour and depleted it of T-reg cells, which resulted in an 'immunological abscopal effect' on distant metastases and in the establishment of long-term memory that impeded tumour recurrence. We also show that the scaffold can be used to deliver tumour-antigen-specific T cells into the tumour. Peritumourally implanted immunomodulatory scaffolds may represent a general strategy to enhance T-cell immunity and avoid the toxicities of systemic therapies.

Automated summary

A biodegradable macroporous scaffold implanted peritumourally releases inhibitors to suppress T-reg cells and attract and stimulate effector T cells, resulting in enhanced immune response, clearance of tumour cells, and prevention of recurrence. The scaffold can also deliver tumour-antigen-specific T cells into the tumour. This strategy offers a potential alternative to systemic therapies with reduced toxicities.