What is the strongest evidence that neoantigen vaccines work?
The most compelling human data comes from a phase 1 trial of an mRNA neoantigen vaccine (autogene cevumeran) in pancreatic cancer. At a median follow-up of 3.2 years, patients whose immune systems responded to the vaccine had a median recurrence-free survival that was not yet reached, while non-responders relapsed at a median of 13.4 months [2]. This is a dramatic difference, but it comes from only 16 patients total—8 responders and 8 non-responders—so the numbers are small.
The same trial also showed that vaccine-induced T cells were remarkably long-lived, with an average estimated lifespan of 7.7 years, and some clones predicted to last decades [2]. These T cells persisted at high levels for about 3 years and retained the ability to kill cancer cells, suggesting the vaccine creates a durable immune memory.
Does the evidence hold up across different cancer types?
No—results vary significantly by cancer type. In a liver cancer trial (hepatocellular carcinoma), 8 of 10 high-risk patients who received a personalized neoantigen vaccine still relapsed, with a median recurrence-free survival of only 7.4 months after vaccination [3]. Only the 5 patients who showed a vaccine-induced T-cell response had a statistically significant longer recurrence-free survival compared to matched controls [3]. This tells us that generating an immune response is key, but not all patients mount one.
In contrast, a phase 1/2 trial of a DNA neoantigen vaccine combined with the immunotherapy pembrolizumab in advanced liver cancer reported an objective response rate of 30.6% (11 of 36 patients), with 3 patients achieving a complete response [5]. That is promising, but the trial was single-arm (no placebo group), so it is unclear how much of the benefit came from the vaccine versus the immunotherapy alone. A separate phase 1 trial across multiple cancer types (head and neck, breast, bladder, multiple myeloma) found that 100% of 13 patients developed vaccine-specific T-cell responses, but the abstract does not report how many actually had clinical benefit [4].
Are neoantigen vaccines safe and practical for real-world use?
Yes, across all the trials, the vaccines were well-tolerated with mostly mild side effects like injection-site reactions [1][3][4][5]. No dose-limiting toxicities or severe treatment-related adverse events were reported in the liver cancer trial combining a DNA vaccine with pembrolizumab [5]. This safety profile is a major reason for the hype—these vaccines are not adding significant toxicity to existing treatments.
Feasibility is also improving. The pancreatic cancer trial showed that personalized mRNA vaccines could be manufactured and administered within 3 days of benchmarked times [1]. A systematic review of 147 clinical trials found that peptide vaccines are the most common type (41%), but mRNA vaccines are growing rapidly, especially in recent trials [6]. This suggests the technology is becoming scalable, though it remains complex and expensive.
About These Sources
This answer is built on 6 peer-reviewed studies — published from 2021 to 2025, 2 from 2024 or later, 4 in Q1 journals, collectively cited 1,456 times — selected as the most relevant from 6 studies that passed quality screening, drawn from 64 papers retrieved from a database of over 500 million.
Sources used in this answer
Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer
In a phase 1 trial of 16 pancreatic cancer patients, the mRNA neoantigen vaccine induced T-cell responses in 8 patients, who had a median recurrence-free survival not reached at 18 months vs. 13.4 months for non-responders (p=0.003).
RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer
At a 3.2-year follow-up of the same pancreatic cancer trial, vaccine-induced T cells had an average lifespan of 7.7 years, and responders still had a significantly longer recurrence-free survival (median not reached vs. 13.4 months, p=0.007).
Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion
In a trial of 10 liver cancer patients, 8 relapsed after neoantigen vaccination; only the 5 patients with vaccine-induced T-cell responses had a significantly longer recurrence-free survival (p=0.035).
Abstract CT270: Immunogenicity of PGV_001 neoantigen vaccine in a Phase-I clinical trial, across various types of cancers in adjuvant setting
In a phase 1 trial across multiple cancer types, all 13 patients developed vaccine-specific T-cell immunity, with 45% of vaccine antigens inducing de novo immune responses.
Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial.
In a phase 1/2 trial of a DNA neoantigen vaccine plus pembrolizumab in 36 advanced liver cancer patients, the objective response rate was 30.6% (11/36), with 3 complete responses; 86.4% of evaluable patients showed T-cell responses.
Neoantigen Vaccines; Clinical Trials, Classes, Indications, Adjuvants and Combinatorial Treatments
A systematic review of 147 neoantigen vaccine clinical trials found peptide vaccines are most common (41%), but mRNA vaccines are growing; the most common cancer types are glioma, lung cancer, and melanoma.