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

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)