In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment
Qian Chen, Chao Wang, Xudong Zhang, Guojun Chen, Quanyin Hu, Hongjun Li, Jinqiang Wang, Di Wen, Yuqi Zhang, Yifei Lu, Guang Yang, Chen Jiang, Jun Wang, Gianpietro Dotti, Zhen Gu
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.