Background: Patients with solid tumor may get benefits from neoantigen-based cancer vaccines, which has showed some clinical efficacy data in clinical trials. This study was designed to evaluate the safety and efficacy of a neoantigen-based dendritic cell vaccine in patients with advanced solid tumors Methods: In this single arm study, patient-specific mutation-containing epitopes were detected from patient's tumor tissue. Tumor specimens were processed for whole transcriptome RNA sequencing, whole exome sequencing and HLA typing analysis. Total 10-20 immunogenic neoantigens for each patient were formulated and loaded into patient’s dendritic cells to manufacture the patient-specific anti-cancer vaccines. The patient was administered vaccine injections (Days 0, 14, 35, 56 and 98) into inguinal lymph nodes and intra-cutaneous. Peripheral blood was collected during the treatment (Days 14,15, 35, 36, 56, 57,77, 99 and 120) for safety evaluation and for assessment of the expansion of antigen-specific T cells in vivo. Patients were followed up until confirmed disease progression, withdrawal consent or adverse event intolerance. Results: Between 2019 and 2020, six patients received the neoantigen-based DC vaccine. The tumor types were laryngeal carcinoma, leiomyosarcoma, biliary tract carcinoma and hepatocellular carcinoma. All six enrolled patients had stage III or IV disease and had failed at least one line of systematic therapy at baseline. Preliminary data revealed that 6 pts (5 female and 1 male) with mean age of 44 (41-50) yrs. received ≥3 dose of DC vaccine. Doses ranged from 2×10⁶ cells/ml to 10×10⁶ cells/ml. All observed treatment related Adverse Events were Grade 1 or Grade 2. The most common (≥10%) drug-related adverse events were fatigue (15%), fever (15%), and elevated AST (20%). Five patients received at least one disease assessment post baseline visit. There were no tumor response. The patient with biliary tract carcinoma, laryngeal ca, leiomyosarcoma had SD status for 11 weeks, 30 weeks and 16 weeks respectively. Patients were assessed with the ELISPOT, which showed a CD8 + neoantigen-specific T-cells expansion was detected from each of the six patients’ peripheral blood after the fifth vaccine injection, which demonstrate the preliminary proof of concept for this personalized neoantigen-based dendritic cell vaccine. Conclusions: In this study, neoantigen-based dendritic cell vaccine has showed preliminary activity in advanced solid tumor patients with well-tolerated safety profile, which indicated the neoantigen-targeting DC vaccine has potential to be an effective treatment (with alteration of the immune cell milieu) in solid tumor patients.