Safety and Preliminary Efficacy of Personalized Neoantigen-pulsed Dendritic Cell Vaccination in Patients With Solid...

Immune checkpoint inhibitors have improved outcomes in several malignancies; however, their efficacy remains limited in many solid tumors. Personalized cancer immunotherapy targeting tumor-specific neoantigens represents a promising strategy. We conducted an interim analysis to evaluate the tolerability and preliminary efficacy of neoantigen-pulsed dendritic cell (Neo-DC) vaccination in patients with advanced solid tumors.

Patients with histologically confirmed solid malignancy, Eastern Cooperative Oncology Group performance status 0-1, preserved organ function, and who also provided written informed consent were enrolled. Tumor-specific neoantigens were identified by applying next-generation sequencing of tumor tissue, and selected peptides with high predicted MHC class I/II affinity and sufficient expression levels were pulsed with autologous dendritic cells generated from peripheral blood mononuclear cells. Neo-DCs were administered every 2-3 weeks for up to six cycles, with additional doses permitted. Safety, clinical outcomes, overall survival (OS), and immune cell profiles were evaluated.

As of November 2025, 36 patients were registered, and 27 received Neo-DC vaccination and were evaluable. No treatment-related or immune-related adverse events (irAEs) of grade ≥2 were observed, and all irAEs were CTCAE grade 1. The disease control rate (complete response + partial response + stable disease) was 44.4%. The median OS was not reached at the time of analysis. The OS tended to be longer in patients achieving disease control, whereas concomitant chemotherapy showed a nonsignificant trend toward shorter survival. Immunophenotyping demonstrated a significant reduction in regulatory T cells after Neo-DC treatment.

Neoantigen-pulsed dendritic cell vaccination was well tolerated and showed encouraging signs of clinical activity in patients with solid tumors. Modulation of the immunosuppressive tumor microenvironment, reflected by the decreased count of regulatory T cells, may contribute to disease control. Further prospective studies are warranted.