本文由小咖机器人翻译整理

期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-023-02760-3

摘要内容如下：

胰腺癌和结直肠癌通常是KRAS突变的，并且当肿瘤DNA或蛋白质持续存在或在治疗性治疗后复发时是不可治愈的。癌症疫苗Eli-002 2P使用G12D和G12R突变KRAS（MKRAS）肽（AMPH-肽-2P）的两亲物（AMPH）修饰与CpG寡核苷酸佐剂（AMPH-CpG-7909）一起增强淋巴结递送和免疫应答。在一项固定剂量AMPH-肽-2P和递增剂量AMPH-CpG-7909的1期研究中，我们治疗了25例（20例胰腺和5例结直肠）患者，这些患者在局部区域治疗后微小残留mKRAS疾病（ctDNA和/或血清肿瘤抗原）阳性。研究招募已完成，患者随访正在进行中。主要终点包括安全性和推荐的2期剂量（RP2D）。次要终点是肿瘤生物标志物反应（纵向ctDNA或肿瘤抗原），探索性终点包括免疫原性和无复发生存率（RFS）。未观察到剂量限制性毒性，AMPH-CpG-7909的RP2D为10.0mg。在25名患者中的21名中观察到直接的离体MKRAS特异性T细胞应答（84%；59%（CD4+和CD8+）；25名患者中有21名（84%）观察到肿瘤生物标志物反应；25名患者中有6名（24%）观察到生物标志物清除；三个胰腺和三个结肠直肠）；中位RFS为16.33个月。疗效与T细胞应答高于或低于基线（12.75倍）增加的中位数倍数相关：肿瘤生物标志物降低的中位数分别为-76.0%和-10.2%（P<0.0014），未达到RFS的中位数分别为4.01个月和4.01个月（风险比=0.14；P=0.0167）。Eli-002 2P是安全的，并且在患有免疫治疗顽固性KRAS突变肿瘤的患者中诱导了相当大的T细胞应答。

英文原文如下：

Abstracts

Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing. Primary endpoints included safety and recommended phase 2 dose (RP2D). The secondary endpoint was tumor biomarker response (longitudinal ctDNA or tumor antigen), with exploratory endpoints including immunogenicity and relapse-free survival (RFS). No dose-limiting toxicities were observed, and the RP2D was 10.0 mg of Amph-CpG-7909. Direct ex vivo mKRAS-specific T cell responses were observed in 21 of 25 patients (84%; 59% both CD4+ and CD8+); tumor biomarker responses were observed in 21 of 25 patients (84%); biomarker clearance was observed in six of 25 patients (24%; three pancreatic and three colorectal); and the median RFS was 16.33 months. Efficacy correlated with T cell responses above or below the median fold increase over baseline (12.75-fold): median tumor biomarker reduction was -76.0% versus -10.2% (P < 0.0014), and the median RFS was not reached versus 4.01 months (hazard ratio = 0.14; P = 0.0167). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors.

-----------分割线---------

点击链接：https://www.mediecogroup.com/community/user/vip/categories/ ，成为医咖会员，获取12项专属权益。

现在购买可享受最大优惠（买一年送三个月，买两年送一年），2024年2月10日起将不再享有该优惠。