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

Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

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)

Article activity feed