Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type that arises in the squamous epithelial cells lining of the mucosal surfaces of the upper aerodigestive tract¬. Long term survival of patients with advanced disease stage remains disappointing with current treatment options. We show that tissue factor is abundantly expressed on patient-derived HNSCC cell lines, xenograft tumor material, and tumor biopsies from patients with HNSCC. Tisotumab vedotin (TV) is an antibody-drug conjugate (ADC) directed to tissue factor, a protein expressed in many solid tumors. HNSCC cells and xenograft tumors were efficiently eliminated in vitro and in vivo with TV-monotherapy compared to treatment with a control antibody conjugated to monomethyl auristatin E (MMAE). Anti-tumor activity of TV was also tested in vivo in combination with chemoradiotherapy, standard of care for patients with advanced stage HNSCC tumors outside the oral cavity. Preclinical studies showed that by adding TV to chemoradiotherapy, survival was markedly improved, and TV, not radiotherapy or chemotherapy, was the main driver of anti-tumor activity. Interestingly, TV-induced cell death in xenograft tumors showed an influx of macrophages indicative of a potential immune-mediated mode-of-action. In conclusion, based on these preclinical data, TV may be a novel treatment modality for patients suffering from head and neck cancer and is hypothesized to improve efficacy of chemoradiotherapy.

中文翻译：

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针对组织因子的抗体-药物缀合物作为单一药物以及与放化疗联合使用，在头颈癌中显示出临床前抗肿瘤活性

头颈鳞状细胞癌（HNSCC）是一种实体瘤类型，发生于上呼吸消化道粘膜表面的鳞状上皮细胞内层。对于目前的治疗方案，晚期疾病患者的长期生存率仍然令人失望。我们发现，组织因子在患者来源的 HNSCC 细胞系、异种移植肿瘤材料和 HNSCC 患者的肿瘤活检组织中大量表达。Tisotumab vedotin (TV) 是一种针对组织因子的抗体药物偶联物 (ADC)，组织因子是一种在许多实体瘤中表达的蛋白质。与用单甲基阿里他汀 E (MMAE) 缀合的对照抗体治疗相比，TV 单一疗法在体外和体内均有效消除了 HNSCC 细胞和异种移植肿瘤。TV 的抗肿瘤活性也在体内与放化疗结合进行了测试，放化疗是口腔外晚期 HNSCC 肿瘤患者的护理标准。临床前研究表明，通过在放化疗中加入电视，生存率显着提高，并且电视，而不是放疗或化疗，是抗肿瘤活性的主要驱动力。有趣的是，电视诱导的异种移植肿瘤细胞死亡显示巨噬细胞大量涌入，表明潜在的免疫介导的作用模式。总之，根据这些临床前数据，电视可能是头颈癌患者的一种新型治疗方式，并被认为可以提高放化疗的疗效。