一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
晚期 NSCLC 患者接受抗独特型 NeuGcGM3 疫苗治疗：长期生存者的免疫相关性
英文原题：Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors.
查看英文原题
Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors.
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中文摘要
背景
Racotumomab-alum是一种靶向NeuGcGM3肿瘤相关神经节苷脂的抗独特型疫苗。在晚期癌症患者中的临床试验已证明其低毒性、高免疫原性和临床获益。本研究的目的是确定临床结局的循环生物标志物。
方法
18例IIIb/IV期非小细胞肺癌（NSCLC）患者在一线化疗后接受racotumomab-alum作为转换维持治疗。治疗持续至体能状态严重恶化或出现毒性。通过流式细胞术评估固有免疫和适应性淋巴细胞频率。使用多分析物流式检测试剂盒测定循环因子。
结果
中位总生存期为16.5个月。27%的患者被归类为长期生存者。基线CD4+Tregs和中央记忆（CM）CD8+T细胞频率较低的患者生存期更长。此外，基线NKT细胞频率较高和CD8+T/CD4+Treg比值较高与更长的生存期相关。有趣的是，效应记忆（EM）CD8+T细胞水平显著较低的患者生存期更长。在免疫后样本中，长期生存者与短期生存者相比，NKT细胞和终末效应记忆（EMRA）CD8+T细胞水平更高。正如预期，CD8+T/CD4+Tregs比值在临床获益患者的治疗期间显示显著更高的值。关于血清因子，促肿瘤细胞因子在预后不良患者的治疗期间显著升高。
结论
在接受racotumomab-alum疫苗治疗的晚期NSCLC患者中，较长的生存期可能与基线和治疗期间独特的循环淋巴细胞亚群特征相关。此外，某些促肿瘤相关细胞因子在短期生存者中升高。这些结果应在更大规模的随机临床试验中加以证实。该临床试验已在古巴临床试验注册中心注册（RPCE00000279）。
展开英文摘要原文
Background: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. Clinical trials in advanced cancer patients have demonstrated low toxicity, high immunogenicity and clinical benefit. The goal of this study was to identify circulating biomarkers of clinical outcome. Methods: Eighteen patients with stage IIIb/IV non-small-cell lung cancer (NSCLC) were injected with racotumomab-alum as switch maintenance therapy after first-line chemotherapy.
Treatment was administered until severe performance status worsening or toxicity. The frequencies of innate and adaptive lymphocytes were assessed by flow cytometry. Circulating factors were measured using multi-analyte flow assay kits. Results: The median overall survival was 16. 5 months. Twenty-seven percent of patients were classified as long-term survivors. Patients with lower baseline frequencies of CD4+Tregs and central memory (CM) CD8+T cells displayed longer survival rates.
Furthermore, higher baseline frequencies of NKT cells and a high CD8+T/CD4+Treg ratio were associated with longer survival. Interestingly, patients with significantly lower levels of effector memory (EM) CD8+T cells survived longer. The levels of NKT cells and terminal effector memory (EMRA) CD8+T cells were higher in long-term survivors in comparison with short-term survivors in post-immune samples.
As expected, the ratio of CD8+T/CD4+Tregs showed significantly higher values during treatment in patients with clinical benefits. Regarding serum factors, pro-tumorigenic cytokines significantly increased during treatment in poor survivors. Conclusions : In advanced NSCLC patients receiving racotumomab-alum vaccine, longer survival could be associated with a unique profile of circulating lymphocyte subsets at baseline and during treatment.
Additionally, certain pro-tumor-related cytokines increased in short-term survivors. These results should be confirmed in larger randomized clinical trials. This clinical trial was registered in the Cuban Clinical Trials Register (RPCE00000279).
论文信息
- 作者
- Mazorra Z、Cáceres-Lavernia HH、Nenínger-Vinageras E、Varona-Rodríguez LM、Viada CE、González Z、Rodríguez-Zhurbenko N、Thierry AC
- 单位
- Center of Molecular Immunology, Havana 11600, Cuba.Cuba
- 期刊
- Biomedicines2025 May 6
- 原文标识
- PubMed 40426949 · DOI 10.3390/biomedicines13051122
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