In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment
Menée in vitro et à l'aide de xénogreffes de mélanome sur un modèle murin, cette étude met en évidence l'intérêt d'un gel, administré par spray sur le site de résection lors d'une intervention chirurgicale et contenant des nanoparticules de carbonate de calcium chargées en anticorps anti-CD47, pour réduire le risque de récidive locale et de tumeurs distantes, puis analyse les mécanismes immunologiques impliqués
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.