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在转移性恶性黑色素瘤中,LOAd703诱导的瘤微环境基因工程与阿特佐利祖马布联合使用:一期I/II试验

O Hamid¹, V Ekström-Rydén^2,3, I Mehmi¹

¹The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate, Medical Oncology, Los Angeles, CA, USA.

Nature communications

|February 16, 2026

概括

瘤微环境基因工程与阿特佐利祖马布结合,对抗PD-1抑制剂的黑色素瘤患者显示出有前途. 这种方法增强了免疫激活,并在I/II期试验中导致了持久的反应.

科学领域:

免疫治疗是一种免疫疗法.
在瘤学瘤学.
基因治疗基因治疗

背景情况:

恶性黑色素瘤通常对PD-1抑制具有耐火性,需要新的治疗策略.
瘤微环境 (TME) 调制是克服治疗耐药性的关键领域.

研究的目的:

评估TME基因工程与CD40L和4-1BBL结合阿特佐利祖马布在晚期黑色素瘤中的耐受性和有效性.
评估免疫激活生物标志物和对先前PD-1治疗耐药的患者的临床结果.

主要方法:

一/二期临床试验涉及24名患有第四阶段恶性黑色素瘤的患者.
内注射编码CD40L和4-1BBL的病毒载体,然后进行静脉注射阿特佐利祖马布.
对耐受性,瘤反应 (RECIST 1.1),药理动力学和免疫生物标志物 (TME和血液) 的评估.

主要成果:

组合疗法在两个剂量队列中耐受良好.
在TME和外周血液中都观察到Th1免疫生物标志物的增加.
总体应答率为17%,病例控制率为54%,有46%的患者在两年内还活着. 较低剂量组的中位数无进展生存时间为9.7个月,中位数总生存时间为26.3个月.

结论:

与阿特佐利祖马布 (atezolizumab) 结合的TME基因工程显示出重新敏感化PD-1耐火性黑色素瘤患者或作为单一治疗的潜力.
观察到的免疫激活和有希望的生存数据需要进一步的临床研究.
这项研究强调了将基因疗法与免疫检查点抑制剂结合用于晚期黑色素瘤的潜力.

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