Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma.

ABSTRACT:

Background

Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation.

Methods

We evaluated different GPC2-CAR constructs by measuring the CAR activity in vitro. NOD-SCID mice engrafted orthotopically with human NB cell lines or patient-derived xenografts and treated with human CAR T cells served as in vivo models. Mechanistic studies were pe

SUBMITTER: Sun M 

PROVIDER: S-EPMC9835961 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature