ISA Pharmaceuticals, J.H. Oortweg 19, 2333 CH Leiden, Netherlands.
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
Sci Transl Med. 2020 Mar 18;12(535). doi: 10.1126/scitranslmed.aaz8235.
Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)-induced tumor immunity. We now show the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. Tumor regressions were observed in 43% of 72 evaluable patients. The depletion of myeloid suppressive cells by carboplatin/paclitaxel was associated with detection of low frequency of spontaneous HPV16-specific immunity in 21 of 62 tested patients. Patients mounted type 1 T cell responses to the vaccine across all doses. The group of patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve. This demonstrates that chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action.
治疗性癌症疫苗已有效地诱导了良性癌前致癌人乳头瘤病毒 16（HPV16）诱导的肛门生殖器病变的持久消退。然而，HPV16 诱导的癌症的治疗需要适当的对策来克服癌症诱导的免疫抑制。我们之前表明，标准护理卡铂/紫杉醇化疗可以减少患者中异常高数量的免疫抑制性髓样细胞，从而发展出更强的治疗性 HPV16 疫苗（ISA101）诱导的肿瘤免疫。我们现在在一项剂量评估研究中，在 77 名患有晚期、复发性或转移性宫颈癌的患者中，在化疗期间观察到 ISA101 疫苗接种的临床效果。在 72 名可评估的患者中，有 43%的患者出现肿瘤消退。卡铂/紫杉醇的髓样抑制细胞耗竭与在 62 名测试患者中的 21 名患者中检测到低频率的自发性 HPV16 特异性免疫有关。患者对疫苗产生了 1 型 T 细胞反应，所有剂量均如此。高于中位数的疫苗诱导免疫反应的患者组存活时间更长，生存曲线呈平坦趋势。这表明，基于明确的作用模式，化学免疫疗法可以使晚期癌症患者受益。
