Mazorra Zaima, Cáceres-Lavernia Haslen H, Nenínger-Vinageras Elia, Varona-Rodríguez Leslie M, Viada Carmen Elena, González Zuyen, Rodríguez-Zhurbenko Nely, Thierry Anne-Christine, Suarez-Formigo Gisela María, Ventura-Carmenate Yendry, Baumgaertner Petra, Trabanelli Sara, Jandus Camila, Crombet Tania
Center of Molecular Immunology, Havana 11600, Cuba.
Department of Immunology, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi 23231, United Arab Emirates.
Biomedicines. 2025 May 6;13(5):1122. doi: 10.3390/biomedicines13051122.
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. 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. 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. : 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).
拉科妥单抗 - 明矾是一种靶向NeuGcGM3肿瘤相关神经节苷脂的抗独特型疫苗。晚期癌症患者的临床试验已证明其毒性低、免疫原性高且具有临床益处。本研究的目的是确定临床结局的循环生物标志物。18例IIIb/IV期非小细胞肺癌（NSCLC）患者在一线化疗后接受拉科妥单抗 - 明矾作为转换维持治疗。治疗持续至严重的身体状况恶化或出现毒性反应。通过流式细胞术评估先天性和适应性淋巴细胞的频率。使用多分析物流式检测试剂盒测量循环因子。中位总生存期为16.5个月。27%的患者被归类为长期幸存者。基线时CD4 + Tregs和中枢记忆（CM）CD8 + T细胞频率较低的患者生存率更长。此外，NKT细胞的基线频率较高以及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。与免疫后样本中的短期幸存者相比，长期幸存者的NKT细胞和终末效应记忆（EMRA）CD8 + T细胞水平更高。正如预期的那样，在有临床获益的患者中，治疗期间CD8 + T/CD4 + Tregs的比值显著更高。关于血清因子，在预后较差的幸存者中，促肿瘤细胞因子在治疗期间显著增加。：在接受拉科妥单抗 - 明矾疫苗的晚期NSCLC患者中，更长的生存期可能与基线和治疗期间循环淋巴细胞亚群的独特特征有关。此外，某些促肿瘤相关细胞因子在短期幸存者中增加。这些结果应在更大规模的随机临床试验中得到证实。该临床试验已在古巴临床试验注册中心注册（RPCE00000279）。
