Integrin αvβ3 Targeted Radiopharmaceutical 99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy

WEN Xuejun; ZHOU Wuhao; GUO Zhide; ZHANG Xianzhong

doi:10.12290/xhyxzz.2023-0155

Volume 14 Issue 4

Jul. 2023

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Medical Journal of Peking Union Medical College Hospital > 2023 > 14(4): 766-773. > DOI: 10.12290/xhyxzz.2023-0155

WEN Xuejun, ZHOU Wuhao, GUO Zhide, ZHANG Xianzhong. Integrin α_vβ₃ Targeted Radiopharmaceutical ^99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(4): 766-773. DOI: 10.12290/xhyxzz.2023-0155

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Integrin α_vβ₃ Targeted Radiopharmaceutical ^99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy

1.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian 361102, China
2.
Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
3.
Institute of Clinical Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China

Funds:

National Natural Science Foundation of China 81901805

National Natural Science Foundation of China 21976150

National Natural Science Foundation of China 21906135

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Corresponding author:
GUO Zhide, E-mail: gzd666888@xmu.edu.cn

ZHANG Xianzhong, E-mail: zhangxzh@hotmail.com
Received Date: March 27, 2023
Accepted Date: July 02, 2023
Available Online: July 25, 2023
Issue Publish Date: July 29, 2023

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Abstract

Abstract

Objective To investigate the effect of ^99mTc-labeled RGD peptide (^99mTc-RGD) on regulating the tumor immune microenvironment and enhancing the anti-tumor effect of immunotherapy when combined with anti-programmed death-ligand 1 (PD-L1) antibody.
Methods The expression of PD-L1 on tumor cells was detected by flow cytometry, and the distribution of ^99mTc-RGD in MC38 tumor mice was evaluated using single photon emission computed tomography(SPECT) imaging. The combination therapy was performed to monitor the anti-tumor effect.
Results The expression of PD-L1 on CT26, MC38, 4T1 and B16F10 tumor cells was upregulated after being induced by ^99mTc-RGD, and there was a statistical significance between ^99mTc-RGD treated and untreated groups. Subsequently, SPECT imaging was performed by injecting ^99mTc-RGD into MC38 tumor-bearing mice, and significant tumor uptake was observed. Based on this, the combination of ^99mTc-RGD and anti-PD-L1 antibody in MC38 tumor mice was studied, and the results showed that different doses and time windows had significant effects on the efficacy of the combination therapy. The combination of 18.5 MBq or 37 MBq ^99mTc-RGD with an anti-PD-L1 antibody led to the best therapeutic effect at 4 h intervals.
Conclusions ^99mTc-RGD could induce the upregulation of tumor PD-L1 expression, and when combined with an anti-PD-L1 antibody, it could enhance the anti-tumor effect.
- radiopharmaceuticals,
- PD-L1,
- tumor immunotherapy,
- tumor models

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Integrin α_vβ₃ Targeted Radiopharmaceutical ^99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy

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Integrin α_vβ₃ Targeted Radiopharmaceutical ^99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy