Project description:Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients with high-risk features, such as MYCN aberrations, and relapsed/refractory disease have poor clinical outcomes. This underscores the urgent need for new therapies. Glypican-2 (GPC2) is a MYCN-regulated and recently discovered oncofetal antigen. Given that GPC2 is also expressed in brain tumors, we evaluated the preclinical activity of our GPC2-CAR (CT3-CD28HTM-BBζ) against MB and compared it to two existing CARs targeting GD2 and B7-H3. A newly generated patient-derived xenograft (PDX) MAF1433, with MYCN aberrations, were used to test CAR T-cells in vivo. Single-cell RNA-sequencing were used for mechanistic studies. MB patient samples express intermediate to high levels of GPC2 and can be targeted with a GPC2-CAR, leading to significant in vivo tumor regression in orthotopic tumor models. GPC2-CAR T-cells had equivalent activity to the B7-H3-CAR and enhanced activity compared to the GD2-CAR in vivo. T-cell kinetic studies revealed that GPC2-CAR T-cells home to the TME, expand, and upregulate genes critical for cytotoxicity and T-cell homing to induce MB cell death. CT3-CD28HTM-BBζ GPC2-CAR can regress GPC2+ MB with MYCN aberrations in preclinical studies, providing a preclinical rationale for including children with GPC2+ MB in our upcoming clinical GPC2-CAR T-cell trial.

2025-11-06 | GSE281233 | GEO

Expression of CD22 in Triple-Negative Breast Cancer: A Novel Prognostic Biomarker and Potential Target for CAR Therapy.

Project description: Not available

| S-EPMC9917013 | biostudies-literature

A novel loop-structure-based bispecific CAR that targets CD19 and CD22 with enhanced therapeutic efficacy against B-cell malignancies.

Project description: Not available

| S-EPMC11891134 | biostudies-literature