黑色素瘤
免疫疗法
癌症研究
免疫检查点
医学
肺癌
肿瘤微环境
封锁
细胞毒性T细胞
癌症
免疫系统
抗体
癌症免疫疗法
免疫学
肿瘤科
内科学
生物
体外
受体
生物化学
作者
Julia Boshuizen,Nora Pencheva,Oscar Krijgsman,Daniela D’Empaire Altimari,Patricia Garrido Castro,Beaunelle de Bruijn,Maarten A. Ligtenberg,Elke Gresnigt-Van den Heuvel,David W. Vredevoogd,Ji‐Ying Song,Nils L. Visser,Georgi Apriamashvili,Maarten L. Janmaat,Theo S. Plantinga,Patrick Franken,Mischa Houtkamp,Andreas Lingnau,Maria Jure-Kunkel,Daniel S. Peeper
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2021-02-02
卷期号:81 (7): 1775-1787
被引量:23
标识
DOI:10.1158/0008-5472.can-20-0434
摘要
Abstract Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most patients experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated in therapy resistance and may serve as a marker for therapy-refractory tumors, for example in melanoma, as we previously demonstrated. Here, we show that enapotamab vedotin (EnaV), an antibody–drug conjugate targeting AXL, effectively targets tumors that display insensitivity to immunotherapy or tumor-specific T cells in several melanoma and lung cancer models. In addition to its direct tumor cell killing activity, EnaV treatment induced an inflammatory response and immunogenic cell death in tumor cells and promoted the induction of a memory-like phenotype in cytotoxic T cells. Combining EnaV with tumor-specific T cells proved superior to either treatment alone in models of melanoma and lung cancer and induced ICB benefit in models otherwise insensitive to anti–PD-1 treatment. Our findings indicate that targeting AXL-expressing, immunotherapy-resistant tumors with EnaV causes an immune-stimulating tumor microenvironment and enhances sensitivity to ICB, warranting further investigation of this treatment combination. Significance: These findings show that targeting AXL-positive tumor fractions with an antibody–drug conjugate enhances antitumor immunity in several humanized tumor models of melanoma and lung cancer.
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