Ding, Li, and Zhang et al. report on a clinical trial of a neoantigen-targeted DC vaccine administered to 12 previously treated lung cancer patients. DCs were PBMC-derived, expressed markers of activation and antigen presentation, and were pulsed with a median of 17 predicted neoantigen peptides per patient. The vaccine was safe and induced neoantigen-specific PBMC responses. 9/12 patients experienced disease control following vaccination, with three objective responses. Patients who had previously received immune checkpoint blockade (ICB) therapy displayed improved survival compared to ICB-naive patients.
Contributed by Alex Najibi
ABSTRACT: Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3-14 doses/person). In total, 12-30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.