Nuclear imaging-guided PD-L1 blockade therapy increases effectiveness of cancer immunotherapy.

Journal for Immunotherapy of Cancer
Hannan GaoFan Wang

Abstract

Strategies to improve the responsiveness of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade therapy remain an essential topic in cancer immunotherapy. In this study, we developed a new radiolabeled nanobody-based imaging probe 99mTc-MY1523 targeting PD-L1 for the enhanced therapeutic efficacy of PD-L1 blockade immunotherapy by the guidance of 99mTc-MY1523 SPECT/CT imaging. The binding affinity and specificity of nanobody MY1523 were measured in vitro. MY1523 was radiolabeled with 99mTc by a site-specific transpeptidation of Sortase-A, and the biodistribution and single photon emission CT (SPECT)/CT were performed in mice bearing different tumors. We used interferon-γ (IFN-γ) as an intervention means to establish animal models with different levels of PD-L1 expression, then investigated the ability of 99mTc-MY1523 SPECT/CT for the in vivo non-invasive measurement of PD-L1 expression in tumors. Finally, the PD-L1 blockade immunotherapies guided by 99mTc-MY1523 SPECT/CT were carried out in MC-38, A20, and 4T1 tumor-bearing mouse models, followed by the testing of tumor infiltration T cells. MY1523 exhibited a high binding affinity and specificity to PD-L1 and had no competitive binding with the ther...Continue Reading

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Citations

Jan 21, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Manman LiuYangzhong Liu
Sep 15, 2021·Organic & Biomolecular Chemistry·Fayang XieYefeng Tang

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Methods Mentioned

BETA
biopsy
size exclusion chromatography
ELISA
saturation binding
flow cytometry
FACS
electrophoresis
xenografts

Software Mentioned

Nucline
GraphPad
Prism

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