Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer
Open Access
- 20 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Signal Transduction and Targeted Therapy
- Vol. 6 (1), 1-12
- https://doi.org/10.1038/s41392-020-00448-5
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.Funding Information
- the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University
- the national key Research and Development Program of China
This publication has 47 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- Derivation of HLA types from shotgun sequence datasetsGenome Medicine, 2012
- Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 studyThe Lancet Oncology, 2011
- A scalable, fully automated process for construction of sequence-ready human exome targeted capture librariesGenome Biology, 2011
- Integrative genomics viewerNature Biotechnology, 2011
- Fast and accurate long-read alignment with Burrows–Wheeler transformBioinformatics, 2010
- Dendritic Cell Vaccination Combined with CTLA4 Blockade in Patients with Metastatic MelanomaClinical Cancer Research, 2009
- Gefitinib or Carboplatin–Paclitaxel in Pulmonary AdenocarcinomaThe New England Journal of Medicine, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- Immune epitope database analysis resource (IEDB-AR)Nucleic Acids Research, 2008