| Autor: |
Nan Li, Madeline B. Torres, Madeline R. Spetz, Ruixue Wang, Luyi Peng, Meijie Tian, Christopher M. Dower, Rosa Nguyen, Ming Sun, Chin-Hsien Tai, Natalia de Val, Raul Cachau, Xiaolin Wu, Stephen M. Hewitt, Rosandra N. Kaplan, Javed Khan, Brad St Croix, Carol J. Thiele, Mitchell Ho |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cell Reports Medicine, Vol 2, Iss 6, Pp 100297- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2666-3791 |
| DOI: |
10.1016/j.xcrm.2021.100297 |
| Popis: |
Summary: Targeting solid tumors must overcome several major obstacles, in particular, the identification of elusive tumor-specific antigens. Here, we devise a strategy to help identify tumor-specific epitopes. Glypican 2 (GPC2) is overexpressed in neuroblastoma. Using RNA sequencing (RNA-seq) analysis, we show that exon 3 and exons 7–10 of GPC2 are expressed in cancer but are minimally expressed in normal tissues. Accordingly, we discover a monoclonal antibody (CT3) that binds exons 3 and 10 and visualize the complex structure of CT3 and GPC2 by electron microscopy. The potential of this approach is exemplified by designing CT3-derived chimeric antigen receptor (CAR) T cells that regress neuroblastoma in mice. Genomic sequencing of T cells recovered from mice reveals the CAR integration sites that may contribute to CAR T cell proliferation and persistence. These studies demonstrate how RNA-seq data can be exploited to help identify tumor-associated exons that can be targeted by CAR T cell therapies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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