对癌症转移和免疫疗法反应进行灵敏、非免疫原性的体内成像。

IF 4.1 Q2 CELL BIOLOGY
Joseph R Merrill, Alessandra Inguscio, Taemoon Chung, Breanna Demestichas, Libia A Garcia, Jill Habel, David Y Lewis, Tobias Janowitz, Scott K Lyons
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引用次数: 0

摘要

对表达报告转基因的肿瘤进行非侵入性成像是一种常用的临床前方法,用于研究体内肿瘤的发展和对治疗的反应,因为这种方法能够将肿瘤信号与背景噪声区分开来。然而,所使用的转基因(如萤火虫荧光素酶)具有免疫原性,因此在免疫功能健全的宿主体内表达时会影响结果。鉴于癌症免疫学和免疫疗法是目前最具影响力的研究和治疗开发领域之一,这是一个重要的局限性。在这里,我们介绍一种非免疫原性的临床前肿瘤成像方法。这种方法以表达小鼠碘化钠合体(mNIS)为基础,有助于在免疫功能正常的肿瘤模型中灵敏、非侵入性地检测合成肿瘤细胞,而不会因外源转基因蛋白或选择标记物的表达而产生额外的免疫原性。表达 NIS 的肿瘤细胞会内化伽马射线发射的 [99mTc]pertechnetate 离子,因此可通过 SPECT(单光子发射计算机断层扫描)进行检测。我们利用免疫功能正常的 C57BL/6 小鼠胰腺导管腺癌肝转移模型,证明该技术能够检测早期转移病灶,并利用精确、可量化的全身 SPECT/CT 成像对免疫疗法反应进行纵向评估。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sensitive, non-immunogenic <i>in vivo</i> imaging of cancer metastases and immunotherapy response.

Sensitive, non-immunogenic <i>in vivo</i> imaging of cancer metastases and immunotherapy response.

Sensitive, non-immunogenic <i>in vivo</i> imaging of cancer metastases and immunotherapy response.

Sensitive, non-immunogenic in vivo imaging of cancer metastases and immunotherapy response.

Non-invasive imaging of tumors expressing reporter transgenes is a popular preclinical method for studying tumor development and response to therapy in vivo due to its ability to distinguish signal from tumors over background noise. However, the utilized transgenes, such as firefly luciferase, are immunogenic and, therefore, impact results when expressed in immune-competent hosts. This represents an important limitation, given that cancer immunology and immunotherapy are currently among the most impactful areas of research and therapeutic development. Here we present a non-immunogenic preclinical tumor imaging approach. Based on the expression of murine sodium iodide symporter (mNIS), it facilitates sensitive, non-invasive detection of syngeneic tumor cells in immune-competent tumor models without additional immunogenicity arising from exogenous transgenic protein or selection marker expression. NIS-expressing tumor cells internalize the gamma-emitting [99mTc]pertechnetate ion and so can be detected by SPECT (single photon emission computed tomography). Using a mouse model of pancreatic ductal adenocarcinoma hepatic metastases in immune-competent C57BL/6 mice, we demonstrate that the technique enables the detection of very early metastatic lesions and longitudinal assessment of immunotherapy responses using precise and quantifiable whole-body SPECT/CT imaging.

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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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