CAR-T cell therapy for diffuse intrinsic pontine glioma

• Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial
• Diffuse Intrinsic Pontine Glioma and Chimeric Antigen Receptor T-Cell Therapy: An Emerging Frontier
• IL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors
• CAR T cell therapy for pediatric central nervous system tumors: a review of the literature and current North American trials
• Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities
• CAR T-cell therapy: a potential treatment strategy for pediatric midline gliomas
• In vitro vascular differentiation system efficiently produces natural killer cells for cancer immunotherapies
• B7-H3 in Brain Malignancies: Immunology and Immunotherapy

CAR-T cell therapy represents an emerging and promising approach in the treatment of diffuse intrinsic pontine glioma (DIPG).

Targetable Antigens: Tumor-specific antigens like GD2, HER2, and B7-H3 have been identified on DIPG cells.

Local Delivery: Intracranial delivery of CAR-T cells (via catheter or convection-enhanced delivery) bypasses the BBB.

Immune Activation: CAR-T cells can sustain immune surveillance, potentially overcoming tumor immune evasion.

Preclinical Studies:

CAR-T cells targeting GD2 and HER2 have shown promising preclinical efficacy in DIPG models.

Animal studies have demonstrated significant tumor reduction and extended survival.

CAR-T cell therapy for diffuse intrinsic pontine glioma clinical trials.

Toxicity:

Cytokine release syndrome (CRS) and neurotoxicity remain key risks.

The delicate location of DIPG raises concerns about inflammatory edema.

Downregulation of target antigens can lead to resistance.

Immunosuppressive tumor microenvironment may impair CAR-T cell activity.

Off-tumor effects may occur if targeted antigens are also expressed on healthy tissues.

Time-intensive and personalized nature of CAR-T production.

Multiplex Targeting:

Engineering CAR-T cells to target multiple antigens to prevent tumor escape.

Combination Therapy:

Combining CAR-T cells with checkpoint inhibitors, radiation therapy, or other immunomodulatory agents.

Improved Delivery Systems:

Developing refined intracranial delivery methods to maximize efficacy while minimizing toxicity.

Advances in CAR Design:

4th-generation CAR-T cells, “armored CARs,” with added immune-stimulatory capabilities.