Neoantigen Vaccine Clinical Trials: A 2026 Landscape Overview

By Lociven · NeoantigenLab · July 2026

Figure 1. Neoantigen vaccine clinical trials landscape, 2026.

mRNA-4157 is the most visible neoantigen vaccine program, but it is not the only one. As of 2026, at least a dozen personalized neoantigen vaccine platforms are in clinical development, using different delivery formats, antigen selection strategies, and combination partners. This post surveys the landscape.

Platform types

Neoantigen vaccines differ primarily in how the antigen is delivered:

Platform Example Advantages Limitations
mRNA-LNP mRNA-4157 (Moderna/Merck) Fast manufacturing, strong CD8 response, scalable Cold chain, cost
Long peptide NeoVax (Dana-Farber), RO7198457 (Roche/BioNTech) Both CD4 and CD8 responses, well-characterized Slower manufacturing, adjuvant required
DNA Various phase 1 programs Stable at room temperature, simple manufacturing Lower immunogenicity than mRNA without electroporation
Viral vector BNT111, BNT112 (BioNTech) High immunogenicity, established safety profile Pre-existing immunity to vector, manufacturing complexity
Dendritic cell Various academic programs Direct antigen presentation Autologous manufacturing, high cost, low scalability

Key trials to know

NeoVax (Dana-Farber / Wu lab)
The original personalized neoantigen long peptide vaccine. Phase 1 results in melanoma (2017, Nature) and glioblastoma showed that personalized vaccines could generate neoantigen-specific T cell responses. GBM results were particularly notable — neoantigen-reactive T cells were detected in tumor-infiltrating lymphocytes after vaccination. This is the academic proof-of-concept that informed later commercial programs.

RO7198457 / BNT122 (BioNTech/Roche)
mRNA-based personalized vaccine (different from mRNA-4157, developed independently by BioNTech). Phase 2 data in pancreatic cancer (2023, Nature) showed that 50% of vaccinated patients generated neoantigen-specific T cells and had significantly delayed recurrence compared to non-responders. Pancreatic cancer is a low-TMB tumor — this suggests personalized vaccines may work in settings where checkpoint monotherapy typically fails.

GRANITE (Gritstone bio)
Heterologous prime-boost using adenovirus vector + self-amplifying RNA. Targets shared neoantigens (KRAS mutations) plus personalized neoantigens. Phase 2 data in colorectal and lung cancer ongoing.

ELI-002 (Elicio Therapeutics)
Amphiphile vaccine targeting KRAS mutations (G12D, G12V, G12R, G13D). Lymph node-targeting delivery. Phase 1 results in pancreatic and colorectal cancer showed T cell responses in all patients. Interesting because it targets shared neoantigens — potentially off-the-shelf.

What the trials have in common

Across platforms, several patterns are emerging:

  1. T cell responses are consistently detected. In nearly every trial, the vaccine generates measurable neoantigen-specific T cell responses. This was not obvious before 2016.
  2. CD4 responses matter. Long peptide and mRNA vaccines that generate both CD4 and CD8 responses appear more effective. The role of CD4 T cells in anti-tumor immunity is now a major research focus.
  3. Checkpoint combination is standard. Every current phase 2/3 trial combines the vaccine with anti-PD-1 or anti-PD-L1. No trial has shown strong single-agent vaccine activity in immunologically cold tumors.
  4. Adjuvant setting may be optimal. Minimal residual disease or resected tumor settings (fewer tumor cells to kill, less immunosuppression) appear more favorable than metastatic settings.

Open questions

The field is converging on some answers while opening new questions:

  • How many neoantigens per vaccine are optimal? mRNA-4157 uses up to 34; NeoVax used 20. Is more always better?
  • Should vaccines target CD8 epitopes, CD4 epitopes, or both? Current evidence suggests both are needed for durable responses.
  • Can biomarkers predict who will respond? Pre-existing TIL infiltration, clonal neoantigen burden, and HLA diversity are candidates, but no validated predictive biomarker exists yet.
  • What happens at progression? Do tumors escape by antigen loss, and can the vaccine be re-dosed with new neoantigens?

The next post covers TIL therapy and its relationship to neoantigen biology — how the T cells in a tumor are shaped by neoantigens, and what that means for TIL expansion protocols.

Tags: neoantigen vaccine, mRNA vaccine, clinical trial, BioNTech, Moderna, personalized cancer vaccine, NeoVax, pancreatic cancer, melanoma

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