💉 Cancer Vaccine for Glioblastoma [Neurosurgery Wiki]

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====== 💉 Cancer Vaccine for Glioblastoma ======

A **cancer vaccine for glioblastoma** is an immunotherapy designed to stimulate the immune system to recognize and attack glioblastoma (GBM) tumor cells by targeting **tumor-specific or tumor-associated antigens**.

===== 🧬 Rationale =====

Glioblastoma is a highly aggressive brain tumor with poor prognosis. Traditional therapies offer limited survival benefit. Cancer vaccines aim to:
  * **Induce T cell–mediated immune responses**
  * Promote **immune memory** against tumor recurrence
  * Target **specific tumor antigens** or **neoantigens**
  * Overcome glioma-associated immune suppression

===== 🔬 Types of Glioblastoma Vaccines =====

^ Type                    ^ Description                                                   ^ Example(s)                    ^
| **Peptide Vaccines**     | Short tumor antigen fragments induce antigen-specific T cells | Rindopepimut (EGFRvIII)       |
| **Dendritic Cell Vaccines** | Patient DCs loaded with tumor lysate or peptides ex vivo     | DCVax-L                       |
| **mRNA Vaccines**        | Encode neoantigens in mRNA to trigger T cell activation       | NOA-16 Trial                  |
| **Neoantigen Vaccines**  | Personalized to each patient's unique tumor mutations         | Moderna/BioNTech platforms    |
| **Tumor Lysate Vaccines**| Use whole tumor cell lysate to broaden antigen exposure       | HSPPC-96 (heat-shock protein) |

===== 🎯 Target Antigens in GBM =====

  * **EGFRvIII** – mutant receptor in 25–30% of GBM
  * **IDH1 R132H** – mutation in lower-grade gliomas
  * **WT1**, **SOX2**, **Survivin** – tumor-associated antigens
  * **Personalized neoantigens** – identified through sequencing

===== 🧪 Key Clinical Trials =====

^ Trial Name        ^ Type              ^ Target/Strategy             ^ Phase      ^ Outcome/Status                           ^
| **NOA-16**        | mRNA vaccine      | Personalized IDH1 neoantigens| Phase I     | Safe, immunogenic (93% T cell response)  |
| **AMPLIFY-NEOVAC**| Combo therapy     | IDH1 vaccine + anti–PD-L1    | Phase I     | Ongoing                                  |
| **DCVax-L**       | DC-based vaccine  | Tumor lysate-loaded DCs      | Phase III   | Improved survival in long-term subgroup  |
| **Rindopepimut**  | Peptide vaccine   | EGFRvIII                     | Phase III   | No OS benefit → development discontinued |

===== ⚠️ Challenges =====

  * **Antigen heterogeneity** → not all tumor cells express the same target
  * **Immune suppression** → GBM microenvironment inhibits T cells
  * **HLA restriction** → some vaccines only work for patients with certain HLA types
  * **Time and cost** of personalized vaccine design

===== 🚀 Future Directions =====

  * **mRNA platforms** for rapid personalization and multi-antigen delivery
  * **AI-based neoantigen prediction**
  * **Combination therapies** with:
    - Checkpoint inhibitors (e.g., anti–PD-1)
    - Oncolytic viruses
    - Radiotherapy
  * **Local delivery** methods (e.g., intratumoral injection, hydrogel implants)

===== 🧾 Summary =====

**Cancer vaccines for glioblastoma** represent a promising class of immunotherapy with a growing body of early clinical evidence. Personalized mRNA vaccines and dendritic cell–based strategies are showing **immunogenicity and feasibility**, especially in combination with other treatments. Overcoming immune suppression and tailoring vaccines to tumor evolution are key to their future success.

===== 🔗 Related Pages =====

  * [[Glioblastoma]]
  * [[Glioblastoma Immunotherapy]]
  * [[NOA-16 Trial]]
  * [[AMPLIFY-NEOVAC Trial]]
  * [[Dendritic Cell Vaccines]]
  * [[Personalized mRNA Neoantigen Vaccine]]
  * [[Checkpoint Inhibitors]]