1. Academic Validation
  2. Ultrasound targeting of microbubble-bound anti PD-L1 mAb to enhance anti-tumor effect of cisplatin in cervical cancer xenografts treatment

Ultrasound targeting of microbubble-bound anti PD-L1 mAb to enhance anti-tumor effect of cisplatin in cervical cancer xenografts treatment

  • Life Sci. 2020 Dec 1;262:118565. doi: 10.1016/j.lfs.2020.118565.
Yao Ma 1 Jiaxuan Han 2 Jinjun Jiang 2 Zhiwei Zheng 2 Yandi Tan 2 Chaoqi Liu 3 Yun Zhao 4
Affiliations

Affiliations

  • 1 Medical College of China Three Gorges University, Yichang, China; Department of Ultrasonography, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, China.
  • 2 Medical College of China Three Gorges University, Yichang, China.
  • 3 Medical College of China Three Gorges University, Yichang, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang, China. Electronic address: ctgulcq@163.com.
  • 4 Medical College of China Three Gorges University, Yichang, China. Electronic address: ZY_zhaoyun123@163.com.
Abstract

Aims: Anti-PD-L1 monoclonal antibody (mAb)-conjugated ultrasound (US) lipid-shelled microbubbles (PD-L1-MBs) were successfully synthesized to investigate whether that PD-L1-MBs could enhance anti-tumor effect in combination therapy with cisplatin (CDDP) under ultrasound mediation.

Main methods: Based on affinity between biotin and streptavidin, we prepared microbubbles conjugated with anti-PD-L1 mAb by membrane hydration and mechanical oscillation. A subcutaneous tumor model was established to test the anti-tumor effect and immunological activity of this combination therapy. Bax and Bcl-2 expression were detected by RT-qPCR and Immunohistochemistry. Cells undergoing Apoptosis in tissue section were determined by TUNEL. Proliferation of splenocytes was analyzed by Flow cytometry. A cytotoxic T lymphocyte assay was performed by CTL. Expression of PD-L1 and CD8 in tissue section was examined by immunologfluorescence. Expression of IFN-γ, TNF-α, CD86 and CD80 was also detected by RT-qPCR.

Key findings: We observed that the growth of the subcutaneous tumor was significantly slower in combined group than that in the group treated with either drug or microbubbles. Moreover, higher antitumor activity was observed in the combined group than that in cisplatin alone, which could be reflected by the number of apoptotic cells in tumor tissues and over expression of Bax in the combined group. This combination treatment also exhibited a better immunological activity, increasing the infiltration of CD8+ T cells and the expression of several revelant cytokines.

Significance: The ultrasound lipid-shelled PD-L1-MBs may enhance anti-tumor effects of cisplatin by blocking the PD-L1 site and improving immune function.

Keywords

Cervical cancer; Cispatin; Microbubbles; PD-L1; Ultrasound.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-D0938
    99.01%, Cell Proliferation Fluorescent Probe