CAR T cells targeting tumor-associated exons of glypican 2 regress neuroblastoma in mice.
Cell Rep Med
; 2(6): 100297, 2021 06 15.
Article
em En
| MEDLINE
| ID: mdl-34195677
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
/
Glipicanas
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Receptores de Antígenos Quiméricos
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Anticorpos Monoclonais
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Neoplasias do Sistema Nervoso
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Neuroblastoma
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos