CAR-T cell therapy for diffuse intrinsic pontine glioma [Neurosurgery Wiki]

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====== CAR-T cell therapy for diffuse intrinsic pontine glioma ======

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

===== Rationale =====

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.

===== Recent Advances =====

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.

===== Clinical Trials =====

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




===== Challenges and Limitations =====

Toxicity:

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

The delicate location of DIPG raises concerns about inflammatory edema.

===== Tumor Escape Mechanisms =====

Downregulation of target antigens can lead to resistance.

Immunosuppressive tumor microenvironment may impair CAR-T cell activity.

===== Limited Antigen Specificity =====

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

===== Manufacturing Complexity =====

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

===== Future Directions =====

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.