Loading
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.
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.
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.
Shares A randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancers, Neoantigen, Off-the-shelf cancer vaccines, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Lynch syndrome, Inherited risk is mostly unidentified, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Prevention we already have is not deployed.
Shares Inherited risk is mostly unidentified, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Prevention we already have is not deployed, Colorectal cancer.
Shares Lynch syndrome, Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, Clinical Cancer Research, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma, Inherited risk is mostly unidentified, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer.
Shares Cancer interception vaccines for high-risk carriers, Prevention we already have is not deployed.
Shares Heidelberg University Hospital / NCT / DKFZ, German Cancer Research Center (DKFZ).
Shares Lynch syndrome, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer.