Construction and preclinical evaluation of a 124 I-labelled bispecific antibody targeting PD-L1 and PD-L2.

Autor: Yao Y; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China., Ren Y; Guizhou University School of Medicine, Guiyang, Guizhou, 550025, People's Republic of China., Hou X; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China., Wang P; Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China., Zhu J; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China., Liu S; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China., Ma X; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China., Liu T; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China., Yang Z; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China. pekyz@163.com., Zhu H; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China. zhuhuabch@pku.edu.cn., Li N; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Peking University, No. 52 Fu-Cheng Rd, Beijing, 100142, People's Republic of China. rainbow6283@sina.com.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2024 Dec; Vol. 52 (1), pp. 36-47. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1007/s00259-024-06886-5
Abstrakt: Purpose: NB12 is a bispecific antibody that consists of two anti-programmed cell death-ligand 1 (PD-L1) nanobodies and two anti-programmed cell death-ligand 2 (PD-L2) nanobodies. The aim of this study was to design a novel tracer, [ 124 I]I-NB12, targeting PD-L1/2 and perform preclinical evaluations to dynamically monitor PD-L1/2 expression for determining cancer patient responsiveness to ICI therapy.
Methods: NB12 was labelled with the radionuclide 124 I at room temperature (RT). An in vitro binding assay was performed to assess the affinity of [ 124 I]I-NB12 for PD-L1 and PD-L2. Cellular uptake, pharmacokinetic, and biodistribution experiments were performed to evaluate the biological properties. Micro-PET/CT imaging with [ 124 I]I-NB12 was conducted at different time points. Immunohistochemical and haematoxylin and eosin (HE) staining experiments were carried out using tumour tissues. Routine blood, biochemical indices and major organ pathology were used to evaluate the biosafety of the tracers.
Results: The radiochemical yield of [ 124 I]I-NB12 was 84.62 ± 3.90%, and the radiochemical purity (RCP) was greater than 99%. [ 124 I]I-NB12 had a high affinity for the PD-L1 (Kd = 19.82 nM) and PD-L2 (Kd = 2.93 nM). Cellular uptake experiments confirmed that the uptake of [ 124 I]I-NB12 by A549-PDL1/2 cells was greater than that by A549 cells. The half-lives of the distribution phase and elimination phase were 0.26 h and 4.08 h, respectively. Micro-PET/CT showed significant [ 124 I]I-NB12 uptake in the tumour region of A549-PDL1/2 tumour-bearing mice compared with A549 tumour-bearing mice 24 h postinjection. Immunohistochemical and HE staining experiments confirmed that tumour-bearing mice was successfully constructed.
Conclusion: We constructed a bispecific antibody that targets PD-L1 and PD-L2, namely, [ 124 I]I-NB12. Biological evaluation revealed its specificity and affinity for PD-L1/2, and micro-PET/CT confirmed the feasibility of visualizing tumour PD-L1/2 in vivo. Using [ 124 I]I-NB12 may be a promising strategy for identifying cancer patients that can potentially benefit from ICI therapy.
Competing Interests: Declarations. Ethics approval: All animal experiments were performed according to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and approved by the Animal Care and Ethics Committee of Peking University Cancer Hospital (Approval No. EAEC 2022-01). Conflict of interest: The authors have no relevant financial or non-financial interests to disclose.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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