What does the best-case evidence show?
In the most striking single result, a 2023 phase 1 trial of a personalized mRNA neoantigen vaccine (autogene cevumeran) in pancreatic cancer found that patients whose immune systems responded to the vaccine had not yet reached median recurrence-free survival at 18 months of follow-up, while non-responders relapsed after a median of 13.4 months [1]. That is a dramatic difference, but it came from only 16 patients, and the vaccine was given alongside chemotherapy and an immunotherapy drug—so the vaccine's independent contribution is unclear.
A 2025 phase 1 trial in high-risk kidney cancer reported that none of the 9 vaccinated patients had a recurrence at a median follow-up of 40 months after surgery [5]. All 9 generated T-cell responses against their tumors, including against key cancer driver mutations. While this sounds remarkable, the study had no control group, so it is impossible to know how many of those patients would have stayed cancer-free without the vaccine.
In advanced liver cancer, a phase 1/2 trial of a DNA neoantigen vaccine combined with the immunotherapy pembrolizumab produced an objective response rate of 30.6% (11 of 36 patients), with 8.3% achieving complete responses [4]. This is better than the 14–17% response rate typically seen with pembrolizumab alone in liver cancer, but again, the trial was single-arm and small.
Why aren't these vaccines in routine use yet?
The central problem is that most trials are too small and lack control groups to prove the vaccine itself causes the benefit. Across the 12 studies reviewed here, the largest enrolled only 36 patients [4], and many had no placebo or standard-treatment comparison. Without randomized controlled trials, it is impossible to rule out that patients who respond well to the vaccine would have done well anyway due to other treatments or favorable biology.
Another major barrier is manufacturing complexity and cost. Each vaccine must be custom-made for each patient based on their tumor's genetic mutations, a process that takes weeks and costs well over $100,000 per dose [6]. This makes large-scale production and routine use impractical with current technology.
Even when vaccines generate immune responses, not all patients benefit. In the pancreatic cancer trial, only half of patients (8 of 16) mounted a strong T-cell response to the vaccine [1]. In a liver cancer study, 5 of 7 patients who received all planned doses showed T-cell responses, but the other 2 did not, and their cancer recurred sooner [2]. The vaccines clearly work better in some patients than others, and we do not yet know how to predict who will respond.
What would it take for neoantigen vaccines to become routine?
First, large randomized phase 3 trials are needed to prove that adding a neoantigen vaccine to standard treatment improves survival or recurrence rates. The most advanced candidate, mRNA-4157 (V940) for melanoma, is already in a phase 3 trial after a phase 2b study showed a 44% reduction in recurrence risk when combined with pembrolizumab [6]. If that trial succeeds, it could pave the way for regulatory approval in melanoma within a few years.
Second, manufacturing must become faster and cheaper. Current personalized vaccine production takes 4–8 weeks, which is too slow for patients with aggressive cancers. New platforms using 'off-the-shelf' vaccines targeting shared mutations (like KRAS) or faster manufacturing methods are being explored [6][8].
Third, better biomarkers are needed to identify which patients are most likely to benefit. Studies show that patients with pre-existing immune fitness—measured by their ability to respond to unrelated vaccines like the COVID-19 shot—may be better candidates [1]. Combining vaccines with other immunotherapies (checkpoint inhibitors, adoptive cell therapy) also appears critical, as the vaccines alone rarely shrink tumors [3][4][7].
About These Sources
This answer is built on 9 peer-reviewed studies — published from 2021 to 2025, 3 from 2024 or later, 5 in Q1 journals, collectively cited 2,348 times — selected as the most relevant from 12 studies that passed quality screening, drawn from 60 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, a personalized mRNA neoantigen vaccine induced strong T-cell responses in half of patients, and those responders had not reached median recurrence-free survival at 18 months vs. 13.4 months in non-responders.
Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion
In 10 liver cancer patients at high risk of recurrence, a personalized neoantigen vaccine was safe and induced T-cell responses in 5 of 7 fully vaccinated patients; responders had significantly longer recurrence-free survival than non-responders.
453 Personalized DNA neoantigen vaccine (GNOS-PV02) in combination with plasmid IL-12 and pembrolizumab for the treatment of patients with advanced hepatocellular carcinoma
In a phase 1/2 trial of a personalized DNA vaccine (GNOS-PV02) plus pembrolizumab in 12 advanced liver cancer patients, the objective response rate was 25% (3 partial responses), with no dose-limiting toxicities.
Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial.
In an expanded phase 1/2 trial of the same DNA vaccine plus pembrolizumab in 36 advanced liver cancer patients, the objective response rate was 30.6% (11 of 36), with 8.3% complete responses; neoantigen-specific T-cell responses were confirmed in 86.4% of evaluable patients.
A neoantigen vaccine generates antitumour immunity in renal cell carcinoma
In a phase 1 trial of a personalized neoantigen vaccine in 9 high-risk kidney cancer patients, none had recurred at a median 40-month follow-up; all generated T-cell responses, including against driver mutations like VHL and PBRM1.
mRNA Cancer Vaccines: A New Paradigm for Personalized Immunotherapy
A review article notes that the mRNA-4157/pembrolizumab combination reduced melanoma recurrence risk by 44% in a phase 2b trial, but manufacturing costs exceed $100,000 per dose, and challenges include tumor heterogeneity and immunosuppressive microenvironments.
369 Concurrent neoantigen vaccination enhances the antitumor effect of dysfunctional T cells during cell therapy
In mouse models and a human melanoma patient, concurrent neoantigen vaccination rescued the poor antitumor effect of adoptive cell therapy using dysfunctional T cells, improving T-cell persistence and tumor regression.
Neoantigens: promising targets for cancer therapy
A review article summarizes that neoantigens are highly immunogenic and tumor-specific targets for personalized cancer immunotherapies, but challenges remain in identification, prediction, and clinical translation.
Challenges in developing personalized neoantigen cancer vaccines
A review article notes that despite over 100 clinical trials of neoantigen vaccines, proof of unequivocal efficacy has remained elusive for most, due to obstacles in vaccine design and the tumor microenvironment.