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.

治疗性癌症疫苗有效地诱导了恶性前致癌性人类乳头瘤病毒16型（HPV16）引起的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，以克服癌症诱导的免疫抑制。我们以前曾证明，标准的卡铂/紫杉醇化疗可以减少患者体内异常大量的免疫抑制性骨髓细胞，从而可以开发出更强的治疗性HPV16疫苗（ISA101）诱导的肿瘤免疫力。现在，我们在ISA101剂量评估研究中显示了77例晚期，复发或转移性宫颈癌患者在化疗期间进行ISA101疫苗接种的临床效果。72名可评估患者中有43％观察到肿瘤消退。卡铂/紫杉醇对骨髓抑制细胞的耗竭与在62位接受测试的患者中检测到低频率的自发HPV16特异性免疫有关。患者在所有剂量下均对疫苗产生1型T细胞应答。疫苗诱导的免疫应答高于中值的患者组的寿命更长，生存曲线尾巴平坦。这表明基于确定的作用方式，可以利用化学免疫疗法使晚期癌症患者受益。在生存曲线上尾巴平坦。这表明基于确定的作用方式，可以利用化学免疫疗法使晚期癌症患者受益。在生存曲线上尾巴平坦。这表明基于确定的作用方式，可以利用化学免疫疗法使晚期癌症患者受益。