A personalized mRNA neoantigen vaccine is a cutting-edge cancer immunotherapy designed to stimulate a targeted immune response against neoantigens—unique tumor-specific mutations—using messenger RNA (mRNA) technology.

1. **[[Tumor biopsy]] and [[sequencing]]** → identify patient-specific mutations
2. **Bioinformatic prediction** → select immunogenic neoantigens
3. **[[mRNA synthesis]]** → encode selected neoantigens
4. **Delivery** → Inject the mRNA (typically in lipid nanoparticles)
5. **Immune activation**:
   - Host cells translate mRNA into neoantigen peptides
   - Peptides are presented via MHC I and II
   - Activation of **CD8⁺ cytotoxic T cells** and **CD4⁺ helper T cells**

• Personalized → tailored to the unique mutations of each patient
• Specific and safe → minimal risk of autoimmunity
• Flexible and rapid production pipeline
• Non-integrating → lower genomic risk
• Suitable for combination with checkpoint inhibitors

• NOA-16 Trial (Glioblastoma, Germany)
  1. First-in-human personalized mRNA neoantigen vaccine
  2. Induced T cell responses, well-tolerated
• Moderna mRNA-4157 + pembrolizumab
  1. Phase II trial in melanoma showed reduced risk of recurrence
• Platforms under development by BioNTech, CureVac, Moderna

1. Requires tumor sequencing and rapid bioinformatic analysis
2. Logistically complex: personalized production per patient
3. Costly, though expected to improve with automation
4. Tumor immune evasion and heterogeneity remain issues

• Integration with AI for neoantigen selection
• Expansion into preventive oncology (e.g., hereditary cancer syndromes)
• Combination with:
  1. Checkpoint inhibitors
  2. Oncolytic viruses
  3. Radiotherapy

The personalized mRNA neoantigen vaccine represents a revolutionary approach in oncology. By leveraging tumor-specific mutations and mRNA technology, it delivers precise, patient-specific immunity with the potential to transform the treatment of highly aggressive and heterogeneous tumors such as glioblastoma and melanoma.