Abstract 3107
Background
Recent genomic and bioinformatic technological advances have made it possible to dissect the immune response to personalized neoantigens encoded by tumor-specific mutations. However, rapid and efficient identification of neoantigens is still fraught with difficulty, and a systematic evaluation of personalized neoantigens based immunotherapy in advanced refractory epithelial tumors is lacking.
Methods
Tumor and ctDNA samples from 16 advanced epithelial cancer patients were underwent mutational profiling by cancer-associated genes panel. Neoantigens identification were performed by two strategies:(1) As classic mode, somatic mutations were subjected to in silico analysis to predict potential high-affinity epitopes and mutated peptides were denovo synthesized; (2) Hotspot mutations were matched to our customized driver mutation-derived neoantigens peptide library. Candidate neoepitopes were identified. Approximately 108 neoantigen loaded DC vaccine and 1010 bulk T cells composed of 109 neoantigen reactive CD8+T cells were generated for personlized immunotherapy.
Results
Among the sequenced patients, 1∼2 neoantigens recognized by autologous T cells have been successfully identified in 3 of 4 patients who utilized the classic mode and 6 of 12 patients who performed customized neoantigens library, respectively. Subsequently, a total number of 6 patients received immunotherapy targeting personalized neoantigen following immunomodulatory chemotherapy or radiotherapy. One patient with metastatic thymoma is achieving a complete and durable response beyond 12 months. In addition, immune related partial response was observed in another advanced pancreatic cancer patient. The remaining 4 patients achieved prolonged stabilization of disease with median PFS of 8.6 months.
Conclusions
Our costomized neoantigens library can provide a novel approach for neoantigens screening in advanced epithelial cancer patients. Besides, targeted sequencing is sufficient for somatic variant and neoantigen identification. The combination of two strategies can accelerate the neoantigen-based translational immunotherapy research into the paradigm of precision medicine.
Clinical trial identification
Legal entity responsible for the study
Baorui Liu
Funding
None
Disclosure
All authors have declared no conflicts of interest.