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TitleCAR T cells targeting tumor-associated exons of glypican 2 regress neuroblastoma in mice.
Journal, issue, pagesCell Rep Med, Vol. 2, Issue 6, Page 100297, Year 2021
Publish dateJun 15, 2021
AuthorsNan 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 /
PubMed AbstractTargeting 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. ...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.
External linksCell Rep Med / PubMed:34195677 / PubMed Central
MethodsEM (single particle)
Resolution21.0 Å
Structure data

25708

7t62

EMDB-25708, PDB-7t62:
GPC2 HEP CT3 complex
Method: EM (single particle) / Resolution: 21.0 Å

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsIMMUNE SYSTEM / Glypican-3 complex

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