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人源化 CD36(hCD36)小鼠模型支持针对 CD36 的治疗候选药物的临床前评估。

Humanized CD36 (hCD36) mouse model supports the preclinical evaluation of therapeutic candidates targeting CD36.

机构信息

Biocytogen Pharmaceuticals (Beijing), 12 Baoshen South Street, Daxing District, Beijing 102600, P.R. China.

Jiangxi University of Chinese Medicine, No. 1688, Meiling Avenue, Xinjian District, Nanchang, Jiangxi 330004, P.R. China.

出版信息

Exp Anim. 2023 Nov 9;72(4):535-545. doi: 10.1538/expanim.23-0021. Epub 2023 Jul 6.

DOI:10.1538/expanim.23-0021
PMID:37407484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10658083/
Abstract

CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates lipid uptake, advanced oxidation protein products, and immunological recognition, and has roles in lipid accumulation, apoptosis, as well as in metastatic colonization in cancer. CD36 is involved in tumor immunity, metastatic invasion, and therapy resistance through various molecular mechanisms. Targeting CD36 has emerged as an effective strategy for tumor immunotherapy. In this study, we have successfully generated a novel hCD36 mouse (Unless otherwise stated, hCD36 mouse below refer to homozygous hCD36 mouse) strain where the sequences encoding the extracellular domains of the mouse Cd36 gene were replaced with the corresponding human sequences. The results showed that the hCD36 mice only expressed human CD36, and the proportion of each lymphocyte was not significantly changed compared with wild-type mice. Furthermore, CD36 monoclonal antibody could significantly inhibit tumor growth after treatment. Therefore, the hCD36 mouse represent a validated preclinical mouse model for the evaluation of tumor immunotherapy targeting CD36.

摘要

CD36(也称为清道夫受体 B2)是一种多功能受体,可介导脂质摄取、高级氧化蛋白产物和免疫识别,并在脂质积累、细胞凋亡以及癌症转移定植中发挥作用。CD36 通过多种分子机制参与肿瘤免疫、转移侵袭和治疗耐药。靶向 CD36 已成为肿瘤免疫治疗的有效策略。在这项研究中,我们成功地构建了一种新型 hCD36 小鼠(除非另有说明,以下 hCD36 小鼠均指纯合 hCD36 小鼠)品系,该品系小鼠 Cd36 基因的细胞外结构域序列被相应的人源序列所取代。结果表明,hCD36 小鼠仅表达人源 CD36,且与野生型小鼠相比,各淋巴细胞比例无明显变化。此外,CD36 单克隆抗体治疗后可显著抑制肿瘤生长。因此,hCD36 小鼠为评估靶向 CD36 的肿瘤免疫治疗提供了一种经过验证的临床前小鼠模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/b7f506f0587c/expanim-72-535-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/ddcd638a5c57/expanim-72-535-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/b7f506f0587c/expanim-72-535-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/ddcd638a5c57/expanim-72-535-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/a05420c0e777/expanim-72-535-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/63846e6b1b0e/expanim-72-535-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/a76f0dc683e2/expanim-72-535-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3990/10658083/b7f506f0587c/expanim-72-535-g005.jpg

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J Exp Med. 2022 Jun 6;219(6). doi: 10.1084/jem.20211314. Epub 2022 Apr 19.
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CD36: an emerging therapeutic target for cancer and its molecular mechanisms.CD36:癌症治疗的新兴靶点及其分子机制。
J Cancer Res Clin Oncol. 2022 Jul;148(7):1551-1558. doi: 10.1007/s00432-022-03957-8. Epub 2022 Feb 27.
3
Lipid droplets: could they be involved in cancer growth and cancer-microenvironment communications?
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Cancer Commun (Lond). 2022 Feb;42(2):83-87. doi: 10.1002/cac2.12257. Epub 2022 Jan 13.
4
Upregulation of CD36, a Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis by Increasing MMP28 and Decreasing E-Cadherin Expression.脂肪酸转运蛋白CD36的上调通过增加MMP28和降低E-钙黏蛋白表达促进结直肠癌转移。
Cancers (Basel). 2022 Jan 5;14(1):252. doi: 10.3390/cancers14010252.
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CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing.CD36 通过 INSIG2 依赖性 SREBP1 加工促进肝细胞从头合成脂肪。
Mol Metab. 2022 Mar;57:101428. doi: 10.1016/j.molmet.2021.101428. Epub 2021 Dec 30.
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