Dual mRNA nanoparticles strategy for enhanced pancreatic cancer treatment and β-elemene combination therapy
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is notoriously immune-resistant, limiting the clinical efficacy of single-agent immune modulators and thereby necessitating the exploration of multimodal immunotherapy combinations. Traditional approaches combining conventional immune checkpoint inhibitors with neoantigen vaccines have shown some promise in treating PDAC but are often compromised by intratumoral T lymphocyte exhaustion and systemic toxicity. Hence, novel approaches are needed to address these challenges. Herein, we demonstrate that mRNA polymeric nanoparticles encoding anti-PD-1 antibodies in situ at the tumor site enhance the therapeutic efficacy of neoantigen-based mRNA vaccine for PDAC. This mRNA-based, in situ anti-PD-1 antibody production strategy also protects tumor-infiltrating T cells from PD-1 inhibition, potentially reducing the toxicities induced by systemic checkpoint inhibition. Our study may provide an innovative dual mRNA nanoparticle strategy for effective tumor neoantigen immunotherapy, as well as an mRNA cancer combination therapy strategy with other clinically approved drugs (e.g., β-elemene).
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (12)
Qianru Zhu
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University
Chuao Yu
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University
Yiquan Chen
Liangzhu Laboratory, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Eye Center of The Second Affliated Hospital, Zhejiang University
Wei Luo
Meng Li
Jianhua Zou
Fan Xiao
Liangzhu Laboratory, Zhejiang University, Zhejiang Provincial Key Lab of Ophthalmology, Eye Center of The Second Affliated Hospital, Zhejiang University
Soohwan An
Center for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital
Qimanguli Saiding
Center for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital
Wei Tao
Center for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital
Na Kong
College of Pharmaceutical Sciences, Liangzhu Laboratory
Tian Xie