Platelets as platforms for inhibition of tumor recurrence post-physical therapy by delivery of anti-PD-L1 checkpoint antibody

Abstract

Cancer local physical therapy (PT) by using heat, cold, electrical stimulation, irradiation or ultrasound to treat tumor is accepted as alternative choice for cancer patients. However, local recurrence and metastasis after such treatments remains to be the major cause of treatment failure and mortality. Therefore, it is necessary to develop a therapeutic strategy to inhibit local recurrence and metastasis. Inspired by the excellent inflammatory targeting ability of platelets, here we expect that the monoclonal antibody against programmed-death ligand 1 (aPDL1) engineered platelets could inhibit tumor local recurrence effectively, by facilitating transport of anti-PD-L1 antibodies to the ablated area with residue tumors. Using triple-negative breast carcinomas (4T1) bearing mouse model, we proved that antibody-coupled platelets could effectively target incompletely ablated tumor with thermal ablation (TA). We found the release of anti-PD-L1 can be triggered upon the platelets activation, together with many pro-inflammatory cytokines. The release of anti-PD-L1 is likely due to the dissociation of platelets upon the activation. Our findings approved that our platelet-based platform could facilitate the delivery of immune checkpoint antibody to tumor residues and remarkably prevent tumor recurrence after ablation. Moreover, this platelet-based delivery strategy may be extended to the targeted delivery of therapeutics post other types of local therapies including photodynamic therapy, high-intensity-focused-ultrasound ablation therapy, and even radiotherapy.

Keywords: Cancer immunotherapy; Cancer recurrence; Controlled release; Drug delivery; Platelets.