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CARTAR:一个使用 TCGA 和 GTEx 数据识别嵌合抗原受体疗法中潜在靶点的全面网络工具。

CARTAR: a comprehensive web tool for identifying potential targets in chimeric antigen receptor therapies using TCGA and GTEx data.

机构信息

Genomic Medicine Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Av. Barcelona, 15706 A Coruña, Spain.

C005, Instituto de Investigación Sanitaria de Santiago (IDIS), Travesía da Choupana, 15706 A Coruña, Spain.

出版信息

Brief Bioinform. 2024 May 23;25(4). doi: 10.1093/bib/bbae326.

DOI:10.1093/bib/bbae326
PMID:38975894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11229032/
Abstract

Chimeric antigen receptor (CAR) therapy has emerged as a ground-breaking advancement in cancer treatment, harnessing the power of engineered human immune cells to target and eliminate cancer cells. The escalating interest and investment in CAR therapy in recent years emphasize its profound significance in clinical research, positioning it as a rapidly expanding frontier in the field of personalized cancer therapies. A crucial step in CAR therapy design is choosing the right target as it determines the therapy's effectiveness, safety and specificity against cancer cells, while sparing healthy tissues. Herein, we propose a suite of tools for the identification and analysis of potential CAR targets leveraging expression data from The Cancer Genome Atlas and Genotype-Tissue Expression Project, which are implemented in CARTAR website. These tools focus on pinpointing tumor-associated antigens, ensuring target selectivity and assessing specificity to avoid off-tumor toxicities and can be used to rationally designing dual CARs. In addition, candidate target expression can be explored in cancer cell lines using the expression data for the Cancer Cell Line Encyclopedia. To our best knowledge, CARTAR is the first website dedicated to the systematic search of suitable candidate targets for CAR therapy. CARTAR is publicly accessible at https://gmxenomica.github.io/CARTAR/.

摘要

嵌合抗原受体 (CAR) 疗法在癌症治疗中取得了突破性进展,利用工程化的人类免疫细胞来靶向和消除癌细胞。近年来,CAR 疗法的兴趣和投资不断增加,强调了其在临床研究中的重要意义,使其成为个性化癌症治疗领域快速发展的前沿。在 CAR 疗法设计中,选择正确的靶点是至关重要的,因为它决定了治疗的有效性、安全性和对癌细胞的特异性,同时避免对健康组织的毒性。在此,我们提出了一套利用来自癌症基因组图谱和基因型组织表达项目的表达数据来识别和分析潜在 CAR 靶点的工具,这些工具在 CARTAR 网站中实现。这些工具侧重于精确定位肿瘤相关抗原,确保靶点的选择性,并评估其特异性,以避免肿瘤外毒性,可用于合理设计双 CAR。此外,还可以使用癌症细胞系中的表达数据来探索候选靶点的表达情况,这些数据来自癌症细胞系百科全书。据我们所知,CARTAR 是第一个专门用于系统搜索适合 CAR 疗法的候选靶点的网站。CARTAR 可在 https://gmxenomica.github.io/CARTAR/ 上公开访问。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/1e520dd5dffe/bbae326f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/6f3b91784f04/bbae326ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/37116e40a86e/bbae326f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/19e7a4c54bed/bbae326f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/c8f187ab3b5f/bbae326f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/1e520dd5dffe/bbae326f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/6f3b91784f04/bbae326ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/37116e40a86e/bbae326f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/19e7a4c54bed/bbae326f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/c8f187ab3b5f/bbae326f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a219/11229032/1e520dd5dffe/bbae326f4.jpg

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DPEP1 promotes drug resistance in colon cancer cells by forming a positive feedback loop with ASCL2.
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