Surgical resection of tumors frequently leaves behind microscopic tumor cells that can lead to recurrence. But researchers have attached an anticancer immunotherapy agent to platelets, which accumulate at surgical margins as part of wound healing — a new strategy aimed at eradicating residual microtumors reported in Nature Biomedical Engineering.1,2
This approach reduced postsurgical tumor recurrence and metastasis in mice with melanoma or triple-negative breast carcinoma, significantly prolonging the animals’ overall survival.
The researchers attached a payload of engineered monoclonal antibodies that target tumors’ programmed-death ligand 1 (PD-L1) proteins to platelets. These anti-PD-L1 antibodies do not attack tumor cells directly; instead, they disable cancer cells’ ability to evade attacks by the patient’s immune cells — a strategy known as immune checkpoint blockade.
Unlike systemic delivery of anti-PD-L1 antibodies, which can sometimes give rise to immune-related adverse events (irAEs) such as autoimmune disease, the conjugate platelet/anti-PD-L1 antibodies are delivered to the surgical site to prompt immune attacks on residual tumor cells.
“We wanted to utilize platelets’ intrinsic tendencies to accumulate at wounds and to interact with circulating tumor cells, for targeted delivery of immune checkpoint inhibitors,” explained coauthor Zhen GU, PhD, of the University of North Carolina at Chapel Hill.
1. Wang C, Sun W, Ye Y, et al. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nature Biomed Engin. 2017 Jan 23. doi: 10.1038/s41551-016-0011 [Epub ahead of print]
2. On target: UNC researcher arms platelets to deliver cancer immunotherapy [news release]. Chapel Hill, NC: University of North Carolina Health Care; January 23, 2017. https://www.eurekalert.org/pub_releases/2017-01/uonc-otu012317.php. Accessed February 7, 2017.