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高活性嵌合抗原受体 T 细胞与间皮素的跨膜区结合，并且不受脱落的间皮素的阻断。

Highly active CAR T cells that bind to a juxtamembrane region of mesothelin and are not blocked by shed mesothelin.

机构信息

Laboratory of Molecular Biology, National Cancer Institute (NCI), Bethesda, MD 20892-4264.

Thoracic and GI Malignancies Branch, NCI, Bethesda, MD 20892.

出版信息

Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2202439119. doi: 10.1073/pnas.2202439119. Epub 2022 May 5.

DOI:10.1073/pnas.2202439119
PMID:35512094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9171807/
Abstract

SignificanceMesothelin (MSLN) is a cell-surface protein that is a popular target for antibody-based therapies. We have identified shed MSLN as a major obstacle to successful antibody therapies and prepared a monoclonal antibody that inhibits shedding and makes very active CAR T cells whose activity is not blocked by shed MSLN and merits further preclinical development.

摘要

意义间皮素（MSLN）是一种细胞表面蛋白，是抗体为基础的治疗的热门靶点。我们已经确定脱落的 MSLN 是成功的抗体治疗的主要障碍，并制备了一种单克隆抗体，抑制脱落，并使非常活跃的 CAR T 细胞，其活性不受脱落的 MSLN 阻断，并值得进一步的临床前开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/cb695d29c2fe/pnas.2202439119fig08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/f7b029e15be6/pnas.2202439119fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/1082119b9ce9/pnas.2202439119fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/affce149c2da/pnas.2202439119fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/1b97e62dcec4/pnas.2202439119fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/1197bdf03b6c/pnas.2202439119fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/6440b62572c1/pnas.2202439119fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/7824eaebed80/pnas.2202439119fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/cb695d29c2fe/pnas.2202439119fig08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/f7b029e15be6/pnas.2202439119fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/1082119b9ce9/pnas.2202439119fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/affce149c2da/pnas.2202439119fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/1b97e62dcec4/pnas.2202439119fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/1197bdf03b6c/pnas.2202439119fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/6440b62572c1/pnas.2202439119fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/7824eaebed80/pnas.2202439119fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c31a/9171807/cb695d29c2fe/pnas.2202439119fig08.jpg

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A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab.
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