Personalized Melanoma mRNA Vaccine Interactive Pipeline & Trial Simulator

1. Patient Somatic Biopsy & HLA-A*02:01 Binding 3 Selected

Patient ID: PT-MEL-8402

Stage: IIIC Resected

HLA Class I: HLA-A*02:01

TMB: 12.4 mut/Mb

Toggle candidate neoepitopes to include in the 34-neoantigen synthetic mRNA transcript. Lower affinity K_d (<50 nM) yields potent TCR recognition:

2. Synthetic mRNA Cassette Construct 5' Cap • Linkers • Poly(A)

m7G-5'UTR — BRAF-V600E •AAY• NRAS-Q61K •AAY• TP53-R248W — 3'UTR-Poly(A)

3. Real-Time Lymph Node Priming & Micrometastasis Clearance Active Surveillance

Dendritic Cell (APC)

Primed CD8+ T-Cell

Residual Melanoma Cell

Perforin / Granzyme Attack

Clonal CD8+ T-Cells

340 / μL

Tumor Micrometastases

4 Cells

Cytotoxic Lysis Rate

92.4%

Epitope Breadth

3 Clones

3-Year Recurrence-Free Survival (RFS) Trial mRNA-4157-P201 / KEYNOTE-942

▬ mRNA Vaccine + Anti-PD1 (RFS: 74.8%) ▬ Anti-PD1 Monotherapy (RFS: 55.6%) ▬ Observation (RFS: 38.2%)

Immunological & Clinical Impact Assessment

Hazard Ratio (HR): 0.56 (95% CI: 0.31–0.98) — 44% Reduction in risk of recurrence or death.

Mechanism of Action: Injected synthetic mRNA encodes patient-specific neoantigens, translated by dendritic cells to prime polyclonal memory CD8+ cytotoxic T-lymphocytes against microscopic distant metastases while Pembrolizumab blocks PD-1 checkpoint exhaustion.

Polyclonality Benefit: Target breadth (3 high-affinity neoepitopes) prevents tumor antigen-loss escape variants compared to single-target modalities.