树突状细胞免疫疗法治疗卵巢癌:我们的成就概览

Onco Pub Date : 2024-03-21 DOI:10.3390/onco4010004
J. Bartůňková
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摘要

上皮性卵巢癌(EOC)是导致女性癌症相关死亡的第五大原因,这在很大程度上反映了这种恶性疾病向腹膜的早期扩散。由于其免疫学特征,EOC 对免疫检查点抑制剂(ICIs)的反应不佳,包括有限的肿瘤突变负荷(TMB)、免疫细胞浸润差以及活跃的免疫抑制。因此,需要新的策略来克服EOC患者经常缺乏原有免疫力的问题。我们开发并测试了一种基于自体树突状细胞(DC)的疫苗(DCVAC),最近在两项招募EOC患者的独立随机II期临床试验(SOV01,NCT02107937;SOV02,NCT02107950)中,该疫苗被证明是安全的,并能显著改善无进展生存期(PFS)。此外,我们的探索性数据分析表明,在TMB低于中位数、CD8+ T细胞浸润减少的EOC患者中,DCVAC的临床疗效更为显著。因此,基于直流电的疫苗是一种很有前景的临床工具,可以启动免疫 "冷 "EOC患者的抗癌免疫。我们的研究结果强调了个性化免疫疗法的必要性以及免疫疗法领域中潜在的肿瘤相关生物标志物的临床意义。还需要进行更多的临床试验来研究这些策略,以及TMB和基线免疫浸润作为生物标志物在指导EOC临床治疗方面的潜在价值。
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Dendritic Cell Immunotherapy for Ovarian Cancer: An Overview of Our Achievements
Epithelial ovarian carcinoma (EOC) is the fifth leading cause of cancer-related death in women, largely reflecting the early dissemination of this malignant disease to the peritoneum. Due to its immunological features, EOC has poor response to immune checkpoint inhibitors (ICIs), including a limited tumor mutational burden (TMB), poor infiltration by immune cells, and active immunosuppression. Thus, novel strategies are needed to overcome the frequent lack of pre-existing immunity in patients with EOC. We developed and tested an autologous dendritic cell (DC)-based vaccine (DCVAC), which has recently been shown to be safe and to significantly improve progression-free survival (PFS) in two independent randomized phase II clinical trials enrolling patients with EOC (SOV01, NCT02107937; SOV02, NCT02107950). In addition, our exploratory data analyses suggest that the clinical benefits of the DCVAC were more pronounced in patients with EOC with lower-than-median TMBs and reduced CD8+ T cell infiltration. Thus, the DC-based vaccine stands out as a promising clinical tool to jumpstart anticancer immunity in patients with immunologically “cold” EOC. Our findings underscore the need for personalized immunotherapy and the clinical relevance of potential tumor-related biomarkers within the immunotherapy field. Additional clinical trials are needed to address these strategies as well as the potential value of the TMB and immune infiltration at baseline as biomarkers for guiding the clinical management of EOC.
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