Abstract 4108: Safety and feasibility of personalized neoantigen DC vaccines in postoperative esophagus squamous cell carcinoma: A Phase 1b trial

Abstract Background: Immunotherapy, currently stands at the forefront of esophagus squamous cell carcinoma (ESCC) research. Yet, the landscape of post-surgical adjuvant therapy, particularly for patients resistant or unresponsive to initial immunotherapy, remains unexplored. Addressing this, our prospective study evaluates the efficacy of a personalized neoantigen-loaded dendritic cell vaccine (Neo-DCVac) as a novel adjuvant in ESCC patients after neoadjuvant immunochemotherapy (nICT). Methods: Neo-DCVac, designed for 12 ESCC patients post-radical mastectomy following nICT. The vaccine regimen included five doses at weeks 1, 2, 4, 6, and 8, followed by bi-monthly boosts for a year. The primary endpoints were safety and immune response post-vaccination, with 1- and 2-year overall survival (OS) and progression-free survival as secondary endpoints. The T-cell response to neoantigen peptides was evaluated using ELISPOT, flow cytometry, ELISA, and single-cell sequencing to investigate the vaccine's mechanism of action. Results: From April 2021 to October 2023, a total of 12 ESCC patients were enrolled. The occurrence of all-grade AEs was 38.5% (5/12), all of grade 1-2, with no dose-limiting toxicities. No treatment interruptions or treatment-related deaths were observed. Till October 27 2023, the median follow-up was 31.2 months. Survival analysis revealed 1-year and 2-year disease-free survival (DFS) and overall survival(OS) rates of 88.3%, 66.7%, and 100.0%, 91.7%, respectively. Patients with diver genes had a longer median DFS (not reached) compared with patients without diver genes (10.8 months, P = 0.001). Post-vaccine immunization, all patients showed a marked increase in peripheral blood T cell subtypes (CD3, CD4, CD8), with significant neoantigen peptide response in 75% (9/12) as evidenced by ELISPOT and ELISA tests. Single-cell sequencing coupled with CoNGA analysis revealed a distinct MAIT cell population, displaying 65 clonotypes and 146 cells with consistent GEX profiles and TCR sequences. GLIPH2 analysis on Neo-Vac immunotherapy patients identified shared peptide-MHC specificities, notably in patient ES0-01, and similar patterns in patients ES0-04 and ES0-07, suggesting T cell expansion and neoantigen-specific responses post-vaccination. Conclusions: The neoantigen DC vaccine demonstrated favorable safety and exhibited notable efficacy in ESCC. Clinical trial information: NCT05023928. Research Sponsor: No. Citation Format: Yueyun Chen, Hua-Shan Shi, Yang Hu, Yong Yuan, Yu-Shang Yang, Heng Xu, Li Yang, Zhen-Yu Ding. Safety and feasibility of personalized neoantigen DC vaccines in postoperative esophagus squamous cell carcinoma: A Phase 1b trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4108.