July 22, 2025

Preventive dendritic cell vaccination induced TGF-βRII frameshift neoantigen-specific T-cells are linked to long-term disease-free survival in Lynch Syndrome patients

IVI. Jolanda M. de VriesRadboud University Nijmegen AAAsima AbidiRadboud University Nijmegen HWHarm WestdorpRadboud University Nijmegen

Key Points

Preventive dendritic cell vaccination induced TGF-βRII neoantigen-specific T cells in Lynch Syndrome patients.
In a trial with 23 participants, 39% developed TGF-βRII-specific T cells without severe adverse events.
Vaccination resulted in long-term disease-free survival, with participants remaining cancer-free for nearly 10 years.
This research suggests the need for innovative cancer prevention strategies in high-risk populations.

Abstract

Abstract Despite compliance to surveillance colonoscopies, patients with Lynch Syndrome (LS) remain at a substantial lifetime risk of developing colorectal cancer, with rates as high as 30–52%. This highlights the need for better cancer prevention strategies. To assess the safety, feasibility, and immunogenicity of a preventive (neo)antigen-based dendritic cell (DC) vaccine, a phase I/II clinical trial was conducted involving 3 LS patients with a recent history of colorectal cancer (CRC) and 20 cancer free LS patients. All participants were HLA-A2+ and received autologous mature DC pulsed with HLA-A2-binding short peptide derived from carcinoembryonic antigen (CEA) and frameshift-derived neoantigens from caspase-5 and TGF-βRII. No grade 4 adverse events occurred in 22/23 patients and (neo)antigen-specific CD8 T cells were detected in nearly all patients. Post-vaccination, patients who developed T cells specific for the TGF-βRII neoantigen (39%) did not develop any LS-associated neoplasia with TGFBR2 mutation and have remained cancer-free for nearly 10 years. (ClinicalTrials.gov identifier- NCT01885702)

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