In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy

Cancer recurrence after surgical resection remains a significant challenge in cancer therapy. Platelets, which accumulate in wound sites and interact with circulating tumour cells (CTCs), can however trigger inflammation and repair processes in the remaining tumour microenvironment. Inspired by this intrinsic ability of platelets and the clinical success of immune checkpoint inhibitors, here we show that conjugating anti-PDL1 (engineered monoclonal antibodies against programmed-death ligand 1) to the surface of platelets can reduce post-surgical tumour recurrence and metastasis. Using mice bearing partially removed primary melanomas (B16-F10) or triple-negative breast carcinomas (4T1), we found that anti-PDL1 was effectively released on platelet activation by platelet-derived microparticles, and that the administration of platelet-bound anti-PDL1 significantly prolonged overall mouse survival after surgery by reducing the risk of cancer regrowth and metastatic spread. Our findings suggest that engineered platelets can facilitate the delivery of the immunotherapeutic anti-PDL1 to the surgical bed and target CTCs in the bloodstream, thereby potentially improving the objective response rate. By targeting the surgical bed and circulating tumour cells, platelets conjugated with an antibody against an immune checkpoint protein prevent tumour recurrence and metastasis following resection of the primary tumour.