PD-1阻断激活新抗原特异性细胞治疗晚期复发非小细胞肺癌的疗效和安全性。

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2025-01-03 DOI:10.1007/s00262-024-03906-z
Yun Qiao, Kaiyuan Hui, Chenxi Hu, Mei Wang, Wen Sun, Liang Liu, Changhong Dong, Xiaodong Jiang
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引用次数: 0

摘要

背景:肿瘤抗原因其较强的免疫原性和肿瘤特异性,已成为一种具有广阔治疗前景和临床应用价值的免疫治疗靶点。抗程序性死亡-1 (PD-1)抗体重新激活T细胞介导的抗肿瘤免疫。因此,我们进行了单组试验,以评估PD-1阻断(Camrelizumab)激活的新抗原特异性细胞疗法(aNASCT)治疗晚期复发非小细胞肺癌(NSCLC)的安全性和有效性(ClinicalTrials.gov NCT03205930)。方法:根据新鲜活检组织和外周血的全外显子组测序和RNA测序,结合生物信息学分析,设计和制备新抗原肽。所有参与者在第8天皮下注射装载新抗原的成熟树突状细胞(mDCs),并在第27天静脉输注由mDCs诱导的PD-1阻断激活的自体细胞毒性T淋巴细胞(ctl),持续28天(4周)。入组的患者接受了至少三个疗程的治疗。通过评价不良反应、无进展生存期(PFS)、总生存期(OS)来评价治疗的安全性和有效性。结果:本研究共纳入13例晚期复发NSCLC患者。所有13例患者均接受了至少3个周期的aNASCT治疗,其中2例患者接受了最多12个周期的治疗。治疗相关不良事件(ae)发生在4/13(30.8%)患者的一过性发热低于38℃。13例入组患者的客观缓解率(ORR)为7 / 13 (53.85%,95% CI 0.29-0.77)。疾病控制率(DCR)为8 / 13 (61.54%,95% CI 0.36 ~ 0.82)。中位PFS为11个月(95% CI 6.1-15.9),中位OS为15个月(95% CI 11.5-18.5)。结论:我们的研究结果表明,aMASCT治疗对晚期复发NSCLC患者具有安全性和免疫原性,提示其在癌症免疫治疗中的潜力。
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Efficacy and safety of PD-1 blockade-activated neoantigen specific cellular therapy for advanced relapsed non-small cell lung cancer.

Background: Due to its strong immunogenicity and tumor specificity, neoplastic antigen has emerged as an immunotherapy target with wide therapeutic prospect and clinical application value. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. So, we conducted single-arm trial to assess the safety and efficacy of PD-1 blockade(Camrelizumab)-activated neoantigen specific cellular therapy (aNASCT) on advanced relapsed non-small lung cancer(NSCLC)(ClinicalTrials.gov NCT03205930).

Methods: Neoantigenic peptides were designed and manufactured according to the whole exome sequencing and RNA sequencing of fresh biopsy tissues and peripheral blood as well as bioinformatics analysis. All participants received subcutaneous injection of mature dendritic cells(mDCs) loaded with neoantigens on day 8 and an intravenous infusion of PD-1 blockade-activated autologous cytotoxic T lymphocytes (CTLs) induced by mDCs on day 27 for a period defined as 28 days (4 weeks). Enrolled patients received at least three cycles of therapy. The safety and efficacy of the treatment were evaluated by evaluating adverse reactions, progression-free survival (PFS), overall survival (OS).

Results: A total of 13 patients with advanced relapsed NSCLC were enrolled in this study. All 13 patients received at least three cycles of aNASCT treatment, of which two patients received at most 12 cycles of treatment. Treatment-related adverse events (AEs) occurred in 4/13 (30.8%)patients with transient fever below 38℃.The objective response rate (ORR) across the 13 enrolled patients was 7 of 13 (53.85%,95% CI 0.29-0.77).The disease control rate (DCR) was 8 of 13 (61.54%,95% CI 0.36-0.82). The median PFS was 11 months (95% CI 6.1-15.9), and the median OS was 15 months(95% CI 11.5-18.5).

Conclusions: Our findings indicate that aMASCT therapy was safety and immunogenicity of patients with advanced relapsed NSCLC, suggesting its promising potential in cancer immunotherapy.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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