Neoantigen-based personalized DC vaccine for lung cancer: An update of translational study.
ABSTRACT
Background: DC vaccine is a promising strategy for cancer therapy. We conducts a personalized, neoantigen-loaded DC therapy trial in advanced NSCLC (NCT02956551 & ChiCTR-ONC-16009100). Here we provide the updated data.
Methods: Advanced lung cancer patients in their later lines of therapy were enrolled. Whole exon dequencing was performed from freshly obtained tumor tissues as well as the peripheral blood, while RNA-seq was performed in tumor-derived RNA. Somatic mutations were submitted ot systematical progream of neoantigen predication, considring personalized MHC affinity, gene expression, tumor herogeneity, and etc. 10-15 peptides with the highest score were synthesized and pulsed in PBMC-dericed DC, which was introduced to patients. All cells were prepared in a GMP workshop. The primary endpoint was safety and toleratility.
Results: Totally 11 patients were enrolled up to now. Most (n = 5) were adenocarcinoma, and the rest were squamous cancer (n = 4) and NET (n = 2). They were heavily treated (lines of previous therapy: 2-5, median 2). 1 patient failed in re-biopsy, 1 lacked candidate neoantigen, and another died rapdily during the preparation of DC vaccine. 8 patient finally received vaccination (n = 6, male; n = 2, female). The number of neoantigens identified from each patient vairied greatly (35-441, median n = 68). Totally 37 times of vaccination was performed (5-17, median 5). The cell infusion was safe and highly tolerable and no significant side effects were observed, even for those with poor performance. The treatment achieved SD in 7 patients, and only 1 with PD. The median PFS was 5.7m (range: 3.8-10.0m). 5 patients are now maintained on therapy.
Conclusions: The neoantigen based personalized DC vaccine is highly tolerable without obvious side effects. The vaccination strategy shows promise in efficacy. Clinical trial information: NCT02956551