7T62

GPC2 HEP CT3 complex

Summary for 7T62

• Entry DOI: 10.2210/pdb7t62/pdb
• EMDB information: 25708
• Descriptor: Glypican-2, CT3 (2 entities in total)
• Functional Keywords: glypican-3 complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 108361.62

Authors

Zhu, J.,Cachau, R.,De Val Alda, N.,Li, N.,Ho, M. (deposition date: 2021-12-13, release date: 2021-12-22, Last modification date: 2024-10-23)

Primary citation

Li, N.,Torres, M.B.,Spetz, M.R.,Wang, R.,Peng, L.,Tian, M.,Dower, C.M.,Nguyen, R.,Sun, M.,Tai, C.H.,de Val, N.,Cachau, R.,Wu, X.,Hewitt, S.M.,Kaplan, R.N.,Khan, J.,St Croix, B.,Thiele, C.J.,Ho, M.
CAR T cells targeting tumor-associated exons of glypican 2 regress neuroblastoma in mice.
Cell Rep Med, 2:100297-100297, 2021

PubMed Abstract: 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.

PubMed: 34195677
DOI: 10.1016/j.xcrm.2021.100297

Experimental method

ELECTRON MICROSCOPY (21 Å)