Internal medicine

Phagocytosis

Immunotherapy

Fibrin

Cancer

Antigen

Antibody

Immunology

CD47

Cancer research

Medicine

Immune system

Cancer cell

Nature Nanotechnology

Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the ‘don’t eat me’ signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel ‘awakens’ the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread. A gel with therapeutic nanoformulation that can be sprayed at the tumour resection site after surgery activates immune response in the tissue microenviroment, inhibiting tumour recurrence and potential metastasis.

In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment