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

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology Pub Date : 2023-09-11 DOI:10.1002/cti2.1467

Naiqing Ding, Qin Liu, Juan Du, Jie Shao, Yang Yang, Ju Yang, Fangjun Chen, Lixia Yu, Baorui Liu, Jia Wei

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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.

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新抗原反应性T细胞个体化辅助免疫治疗胃印戒细胞癌

目的胃印戒细胞癌(SRCC)具有高度侵袭性。III期胃小细胞癌患者通常在根治性手术后2年内肿瘤复发。不幸的是，没有有效的治疗方法来延缓辅助化疗后的复发。我们的研究旨在探讨新抗原反应性T淋巴细胞(nrt)在III期胃SRCC患者中的安全性和有效性。方法对20例接受根治性手术和辅助化疗的III期胃小细胞癌患者进行研究。在辅助化疗之后，他们接受了一到四个周期的个体化新抗原反应性T细胞治疗。主要终点是中位无进展生存期(mDFS)。次要终点是安全性和免疫反应。中位随访时间为41个月(95% CI: 39-42.9个月)。我们的研究结果显示，与之前的研究相比，接受辅助新抗原反应性t细胞免疫治疗的患者表现出延长无病生存期(DFS)和总生存期(OS)的倾向。2年DFS和OS分别达到73.7%和95%，而5年DFS和OS分别为44%和69%。中位DFS为41个月(95% CI: 28.9-53.1个月)，中位OS未达到。此外，细胞免疫治疗后血清IL-2、IL-4、IL-6、IL-10、TNF-α和IFN-γ浓度均显著升高。不良反应轻微。综上所述，nrt辅助免疫治疗具有良好的疗效和可控的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical & Translational Immunology Medicine-Immunology and Allergy

CiteScore

12.00

自引率

1.70%

发文量

审稿时长

13 weeks

期刊介绍： Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.