2. Academic Validation
  3. Local delivery of IL-15 and anti-PD-L1 nanobody by in vitro-transcribed circILNb elicits superior antitumor immunity in cold tumors

Local delivery of IL-15 and anti-PD-L1 nanobody by in vitro-transcribed circILNb elicits superior antitumor immunity in cold tumors

  • Cell Rep Med. 2025 Oct 21;6(10):102413. doi: 10.1016/j.xcrm.2025.102413.
Dun Niu 1,  Xiaozhuang Ma 1,  Junshi Zhu 1,  Liangbo Sun 1,  Shaotong Zhang 1,  Yaran Wu 1,  Meihua Shan 1,  Xufang Dai 2,  Yaling Liao 1,  Dong Liu 1,  Lu Lu 1,  Mingzhen Yang 3,  Quanming Zou 4,  Jiqin Lian 5
Affiliations

Affiliations

  • 1 Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing 400038, China.
  • 2 College of Education and Science, Chongqing Normal University, Chongqing 400047, China.
  • 3 Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing 400038, China. Electronic address: yangmingzhen0807@126.com.
  • 4 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing 400038, China. Electronic address: qmzou2007@163.com.
  • 5 Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing 400038, China. Electronic address: lianjiqin@tmmu.edu.cn.
PMID: 41075789 DOI: 10.1016/j.xcrm.2025.102413
Abstract

The clinical translation of combined immunocytokine (IC) and immune checkpoint inhibitor (ICI) is constrained by relapse of advanced malignancies, systemic toxicities, and prohibitive research and synthesis costs. In this study, the circCV-B3 vector is constructed to enable scarless circular RNA (circRNA) engineering. The circILNb, engineered via the circCV-B3 vector, enables co-encoding of interleukin-15 (IL-15) and anti-PD-L1 nanobody (Nb). The circILNb is purified by biotin-avidin purification system (BAPS) and is encapsulated within lipid nanoparticles (LNPs). Intratumoral circILNb administration achieves in situ protein expression, achieving local tumor control. Furthermore, dendritic cells (DCs) load circILNb and migrate to tumor-draining lymph node (tdLN), where they prime antigen-specific CD8+ T cell activation, eliciting a robust systemic immune response. These findings highlight the potential of circCV-B3 vector and BAPS as a methodology for circRNA engineering and substantiate circILNb as non-protein-based therapeutic strategy for tumor immunotherapy.

Keywords

IL-15; anti-PD-L1 nanobody; biotin-avidin purification system; circCV-B3; circILNb; tumor immunotherapy.

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