# First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers

Source: https://onco.cc/key-papers/paper-lynch-frameshift-vaccine-ccr-2020/  
OnCo record `paper-lynch-frameshift-vaccine-ccr-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A vaccine of three frameshift peptides shared by almost all microsatellite-unstable tumours was safe and induced immune responses in every patient with MSI colorectal cancer, opening the path to cancer interception vaccines for Lynch syndrome.

## Summary

Mismatch-repair-deficient tumours accumulate insertion or deletion mutations in the same coding microsatellites, producing frameshift peptide (FSP) neoantigens that are shared across patients. This phase I/IIa trial vaccinated 22 patients with a history of MSI-high colorectal cancer with three FSP neoantigens (derived from AIM2, HT001 and TAF1B) with Montanide adjuvant.

The vaccine was well tolerated (injection-site reactions only) and induced humoral and cellular immune responses in all patients who completed the schedule. The study established that shared frameshift neoantigens are immunogenic in humans and are candidates for an off-the-shelf preventive vaccine in Lynch syndrome carriers.

It seeded the Nous-209 adenoviral vaccine (209 frameshift neoantigens) now in trials in Lynch carriers, and the NCI's Lynch interception programme.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Clinical Cancer Research
- Year: 2020
- DOI: 10.1158/1078-0432.CCR-19-3517
- Authors: Kloor M, Reuschenbach M, Pauligk C, et al.
- Findings: 22 patients enrolled; no vaccine-related serious adverse events; Humoral and cellular responses to at least one frameshift peptide in all patients who completed the three-vaccination schedule; Frameshift neoantigens targeted are present in the majority of MSI-high colorectal cancers regardless of patient; The paper provided human proof of principle for a shared-antigen interception vaccine
- What it means: Because Lynch syndrome tumours make the same abnormal proteins in almost every patient, a single vaccine could in principle be given to carriers before cancer develops. This small trial showed the concept is safe and immunogenic; whether it prevents cancer requires the randomised trials now being planned.
- Caveats: Immune response, not cancer prevention, was the endpoint; Patients had existing or prior cancers, not healthy carriers; Peptide vaccines with Montanide elicit modest T-cell responses compared with viral-vector or mRNA platforms; Efficacy trials in carriers need thousands of participants and years of follow-up

## Sources

- DOI: https://doi.org/10.1158/1078-0432.CCR-19-3517
- ClinicalTrials.gov NCT05078866: https://clinicaltrials.gov/study/NCT05078866

## Connected records

- ideas: [A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approval](https://onco.cc/ideas/idea-moon-lynch-vaccine-phase3/), [A randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancers](https://onco.cc/ideas/idea-prev-lynch-frameshift-vaccine-rct/), [Cancer interception vaccines for high-risk carriers](https://onco.cc/ideas/idea-interception-vaccines/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/), [Prevention & Risk](https://onco.cc/fronts/prevention/)
- technologies: [Cancer interception vaccines](https://onco.cc/technologies/interception-vaccination/), [Off-the-shelf cancer vaccines](https://onco.cc/technologies/shared-antigen-vaccine/)
- institutions: [German Cancer Research Center (DKFZ)](https://onco.cc/institutions/dkfz/), [Heidelberg University Hospital / NCT / DKFZ](https://onco.cc/institutions/heidelberg-nct/)
- terms: [Lynch syndrome](https://onco.cc/terms/lynch-syndrome/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Neoantigen](https://onco.cc/terms/neoantigen/)
- bottlenecks: [Inherited risk is mostly unidentified](https://onco.cc/bottlenecks/b-hereditary-risk/), [Prevention we already have is not deployed](https://onco.cc/bottlenecks/b-prevention-adoption/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)

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