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

Abstract

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.

Keywords

• adoptive cell immunotherapy
• gastric cancer
• neoantigen‐reactive T cells
• signet‐ring cell carcinoma