In a groundbreaking discovery, researchers at Wake Forest School of Medicine have unveiled a nanoparticle therapeutic that revolutionizes cancer immunotherapy, offering a promising new approach to treating malignant pleural effusion (MPE). MPE, characterized by the accumulation of fluid between the chest wall and lungs, often harbors malignant cells or tumors, posing a significant challenge in cancer management.
Published in the esteemed journal Nature Nanotechnology, the study addresses a critical need in oncology, particularly for the over 200,000 individuals diagnosed with MPE in the United States annually, with non-small cell lung cancer accounting for a substantial portion of cases.
Dr. Dawen Zhao, lead author of the study, underscores the urgency of their findings, stating, “MPE is indicative of late-stage metastatic cancer and is associated with a poor prognosis, with an average survival of only four to nine months. It profoundly impacts patients’ quality of life, causing breathlessness, pain, weight loss, and reduced physical activity.”
While recent clinical trials exploring immune checkpoint inhibitors (ICI) and novel immunotherapies have shown promise in MPE patients, the efficacy remains limited, with many experiencing immunotoxicity. Zhao highlights a critical hurdle, explaining, “MPE harbors abundant tumor-associated immune cells that evade immune recognition, creating a ‘cold’ immune environment resistant to immunotherapy.”
To overcome this challenge, Zhao’s team devised a nanoparticle, liposomal cyclic dinucleotide (LNP-CDN), designed to activate the STING immune pathway selectively. By reprogramming tumor-associated immune cells to mount an anti-tumor response, LNP-CDN aims to transform the immune landscape within MPE.
In mouse models, intrapleural injection of LNP-CDN induced a remarkable shift in the ‘cold’ immune environment, targeting both effusion and pleural tumors within the pleural cavity. Moreover, when combined with anti-PD-L1 immunotherapy, LNP-CDN demonstrated striking efficacy, reducing MPE volume and inhibiting tumor growth in both the pleural cavity and lung tissue, ultimately leading to prolonged survival.
Encouragingly, human MPE tissue samples corroborated these findings, showcasing enhanced tumor cell killing by cytotoxic immune cells upon treatment with LNP-CDN.
Dr. Zhao emphasizes the transformative potential of this nanoparticle therapy, stating, “Administered alone or in conjunction with immunotherapy, our study offers a promising avenue for MPE treatment, addressing the urgent need for interventions to prolong survival and enhance quality of life.”
- Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion. Nature Nanotechnology, 2021; DOI: 10.1038/s41565-021-01032-w
