Individualised adjuvant immunotherapy with neoantigen-reactive T cells for gastric signet-ring cell carcinoma

Abstract

Objectives: The signet-ring cell carcinoma (SRCC) of the stomach is highly invasive. Patients with stage III gastric SRCC usually experience tumor recurrence within 2 years after radical surgery. Unfortunately, there is no effective treatment to postpone recurrence following adjuvant chemotherapy. Our study aimed to explore the safety and efficacy of neoantigen-reactive T lymphocytes (NRTs) in patients with stage III gastric SRCC. Methods: The study included 20 patients with stage III gastric SRCC who received radical surgery and adjuvant chemotherapy. Following the adjuvant chemotherapy, they underwent treatment with a range of one to four cycles of personalised neoantigen-reactive T cells. The primary endpoint was the median progression-free survival (mDFS). The secondary endpoint was safety and immune responses. The median duration of follow-up was 41 months (95% CI: 39–42.9 months). Results: Our results showed that patients who received adjuvant neoantigen-reactive T-cell immunotherapy demonstrated a propensity towards prolonged disease-free survival (DFS) and overall survival (OS) in comparison to previous studies. The 2-year DFS and OS rates reached 73.7% and 95%, respectively, whereas the 5-year DFS and OS rates were 44% and 69%. The median DFS was 41 months (95% CI: 28.9–53.1 months) and the median OS was not reached. In addition, there was a significant increase in serum concentrations of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ after cell immunotherapy. The adverse reactions were mild. Conclusion: In conclusion, adjuvant immunotherapy with NRTs showed promising efficacy alongside a manageable safety profile.