D3-GPC2-Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer.

ABSTRACT:

Purpose

We previously identified glypican 2 (GPC2) as a cell-surface MYCN-regulated neuroblastoma oncoprotein and developed a D3-GPC2 antibody that specifically binds a conformational, tumor-specific epitope conserved between mouse and human.

Experimental design

In this study, we sought to further validate GPC2 as an immunotherapeutic target and develop Investigational New Drug application-enabling data to support the clinical translation of D3-GPC2 chimeric antigen receptor (CAR) T cells.

Results

Immunohistochemistry validated that GPC2 is widely expressed on human neuroblastomas, and flow cytometry showed high levels of cell-surface GPC2 on neuroblastoma cellular models. Second-generation D3-GPC2 CAR T cells with either a 4-1BB or CD28 co-stimulatory domain were sel

SUBMITTER: Giudice AM 

PROVIDER: S-EPMC12699724 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature