Concurrent immune checkpoint blockade for enhanced cancer immunotherapy utilizing engineered hybrid nanovesicles

Yuxuan Liu; Fuxu Yang; Zhimin Li; Ting Wang; Yeteng Mu; Yuxin Fan; Han Xue; Xiuli Hu; Xingang Guan; Hongxia Feng

doi:10.3389/fphar.2024.1487940

Concurrent immune checkpoint blockade for enhanced cancer immunotherapy utilizing engineered hybrid nanovesicles

Front Pharmacol. 2024 Nov 11:15:1487940. doi: 10.3389/fphar.2024.1487940. eCollection 2024.

Authors

Yuxuan Liu^#^{1

2}, Fuxu Yang^#², Zhimin Li^#², Ting Wang³, Yeteng Mu², Yuxin Fan², Han Xue², Xiuli Hu⁴, Xingang Guan³, Hongxia Feng¹

Affiliations

¹ Department of Dermatology, The Affiliated Wenling Hospital of Taizhou University, Taizhou, China.
² College of Medical Technology, Beihua University, Jilin, China.
³ Medical School, Taizhou University, Taizhou, China.
⁴ Institute of Polymer Science and Engineering, School of Chemical Engineering, Hebei University of Technology, Tianjin, China.

^# Contributed equally.

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, demonstrating unprecedented efficacy against advanced cancers. However, their clinical applications are significantly hampered by low overall response rates. Dual blockade of two immune checkpoints represents a promising strategy to enhance immunotherapeutic efficacy. In this study, we developed hybrid cell membrane nanovesicles adorned with PD-1 and SIRPα receptors for combination immunotherapy in melanoma. Our hybrid nanovesicles (PD-1/SIRPα NVs) demonstrated high specificity to PD-L1 and CD47 ligands, facilitating the phagocytosis of melanoma cells by macrophages. In a melanoma mouse model, PD-1/SIRPα NVs significantly suppressed 77% of tumor growth and elicited a robust antitumor immune response for immunotherapy. In conclusion, our findings highlight the promising potential of PD-1/SIRPα NVs as novel and effective ICIs for cancer immunotherapy.

Keywords: PD-1; SIRPα; cancer immunotherapy; cell membrane nanovesicle; immune checkpoint blockade.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by Zhejiang Provincial Natural Science Foundation of China (LY23C100001), Natural Science Foundation of Hebei Province (B2022202029), Zhejiang Provincial Medical and Health Program (2024KY550), Science and Technology Program of Taizhou City (22gya03).