A single dose of heated chemo-immunotherapy for long-term tumor inhibition. (December 2022)

• Record Type: Journal Article
• Authors: Hu, Yingying; Lin, Lin; Guo, Zhaopei; Chen, Jie; Yu, Haiyang; Tian, Huayu; Chen, Xuesi
• Is Part Of: Nano today. Volume 47(2022)
• Publication Date: 2022-12
• Subjects: Single dose -- Mild heat -- Chemo-immunotherapy -- Anti-PD therapy -- Adaptive resistance -- Long-term suppression; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2022.101650
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: The high primary resistance and the following adaptive resistance to therapeutic PD-1/PD-L1 pathway blockade have limited their clinical outcomes. Here, we reported the development of PMJ NPs, the biodegradable nanoparticles for the co-delivery of mitoxantrone (MTO, both chemo drug and photothermal agent) and JQ1 (PD-L1 inhibitor) to achieve mild heated chemotherapy to potentiate anti-PD therapy. Therapeutic regimens of PMJ NPs-based chemo-immunotherapy demonstrated a tumor suppression at early treatment stage but resulted in tumor recurrence later on, and was accompanied by the upregulation of the alternative immune checkpoints for adaptive resistance performance. However, we proved that mild heat (43 ℃) combined therapy led to the enduring tumor remission in both 4T1 and A20 tumor models with only single dose of PMJ NPs. The extra mild heat treatment was confirmed to play a key role for enhanced tumor immunotherapy. Our work provided the single dose of heated chemo-immunotherapy to achieve the long-term tumor suppression might offer a promising regimen for various tumors inhibition in clinics. Graphical Abstract: Mild heated chemotherapy based on minimalist nanoagents (PMJ NPs) was proposed to boost anti-PD therapy. In comparison of chemotherapy, such therapeutics not only improved the initial tumor responses to anti-PD therapy, but also overcome the following adaptive resistance to inhibit tumor relapse, and finally achieved long-term tumor suppression. Mild heated chemotherapy might offer an alternative regimen to replace chemotherapy to promote ICB therapy in clinics. ga1 Highlights: A minimalist and biocompatible nanoagent was proposed for mild heated chemo-immunotherapy. Clinically alternative regimens based on mild heated chemotherapy to enhance ICB therapy. The therapeutics overcome both primary and adaptive resistance to anti-PD therapy to inhibit local tumors and tumor relapse. The therapeutics offered a general strategy for low-immunogenic tumors treatments.