Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
Anticancer Agents Med Chem. 2014 Feb;14(2):190-203. doi: 10.2174/18715206113136660372.
The prognosis of patients with metastatic cervical cancer is poor with a median survival of 8-13 months. Despite the potency of chemotherapeutic drugs, this treatment is rarely curative and should be considered palliative only. The last decades, targeted therapies such as immunotherapy have emerged as an attractive option for the treatment of these patients. Immunotherapy can consist of different modalities such as monoclonal antibodies, adoptive lymphocyte transfer and vaccines, which all are intended to augment the antitumor immune responses in cancer patients. The available evidence indicates that both active and adoptive immunotherapeutical strategies are quite effective against small tumor burdens, but are usually insufficient to eradicate the disease in patients with advanced stages of different kinds of cancer, despite strong induction of tumor-specific immune responses. Although chemotherapy and immunotherapy have not shown to be curative as single modalities, accumulating evidence suggests that combinations of these treatments hold potential for improved clinical outcomes in advanced stages of cancer. Therefore, the combination of chemotherapy and immunotherapy is no longer considered incompatible, because of the emerging insight that certain chemotherapy-based cancer treatments may activate the immune system against the tumor through several molecular and cellular mechanisms. Chemotherapeutic agents and immunotherapy may thus be synergistic and enhance the clinical response. In this review, we show the rationale for combined chemo-immunotherapeutic strategies, and summarize recent data from clinical trials performed in patients with different types of cancer. Challenges such as the selection of the optimal dose and treatment schedule, will be discussed as well as the identification of immune-specific biomarkers. Furthermore, we evaluated the long-term clinical outcomes of patients with advanced cervical cancer treated with HPV16 E6/E7 SLP vaccination with or without chemotherapy. Finally, the future of vaccination therapy in combination with chemotherapy for the treatment of cervical cancer is discussed.
转移性宫颈癌患者的预后较差，中位生存期为 8-13 个月。尽管化疗药物具有强大的作用，但这种治疗很少能治愈，只能被视为姑息性治疗。在过去的几十年中，靶向治疗（如免疫疗法）已成为治疗这些患者的一种有吸引力的选择。免疫疗法可以包括不同的方式，如单克隆抗体、过继性淋巴细胞转移和疫苗，所有这些方式都旨在增强癌症患者的抗肿瘤免疫反应。现有证据表明，主动和过继性免疫治疗策略对小肿瘤负担都非常有效，但通常不足以在不同类型癌症的晚期患者中消除疾病，尽管强烈诱导了肿瘤特异性免疫反应。尽管化疗和免疫疗法作为单一疗法尚未显示出疗效，但越来越多的证据表明，这些治疗方法的联合应用可能会改善晚期癌症患者的临床结局。因此，化疗和免疫疗法的联合应用不再被认为是不相容的，因为新出现的观点认为，某些基于化疗的癌症治疗方法可能通过几种分子和细胞机制激活免疫系统对抗肿瘤。化疗药物和免疫疗法可能因此具有协同作用，并增强临床反应。在这篇综述中，我们展示了联合化疗免疫治疗策略的基本原理，并总结了在不同类型癌症患者中进行的临床试验的最新数据。我们还将讨论诸如最佳剂量和治疗方案的选择等挑战，以及鉴定免疫特异性生物标志物。此外，我们评估了接受 HPV16 E6/E7 SLP 疫苗接种联合或不联合化疗治疗晚期宫颈癌患者的长期临床结局。最后，讨论了疫苗疗法联合化疗治疗宫颈癌的未来。
