O'Dwyer Joanne, O'Cearbhaill Roisin E, Wylie Robert, O'Mahony Saoirse, O'Dwyer Michael, Duffy Garry P, Dolan Eimear B
Department of Biomedical Engineering, School of Engineering, College of Science and Engineering, National University of Ireland Galway, Ireland; Anatomy & Regenerative Medicine Institute, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Ireland.
Anatomy & Regenerative Medicine Institute, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Ireland; Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.
Adv Ther (Weinh). 2020 Nov;3(11). doi: 10.1002/adtp.202000144. Epub 2020 Aug 16.
Ovarian cancer is the most lethal gynecological malignancy with a global five-year survival rate of 30-50%. First-line treatment involves cytoreductive surgery and administration of platinum-based small molecules and paclitaxel. These therapies were traditionally administered via intravenous infusion, although intraperitoneal delivery has also been investigated. Initial clinical trials of intraperitoneal administration for ovarian cancer indicated significant improvements in overall survival compared to intravenous delivery, but this result is not consistent across all studies performed. Recently cell-based immunotherapy has been of interest for ovarian cancer. Direct intraperitoneal delivery of cell-based immunotherapies might prompt local immunoregulatory mechanisms to act synergistically with the delivered immunotherapy. Based on this theory, pre-clinical studies have delivered these cell-based immunotherapies via the intraperitoneal route, with promising results. However, successful intraperitoneal delivery of cell-based immunotherapy and clinical adoption of this technique will depend on overcoming challenges of intraperitoneal delivery and finding the optimal combinations of dose, therapeutic and delivery route. We review the potential advantages and disadvantages of intraperitoneal delivery of cell-based immunotherapy for ovarian cancer and the pre-clinical and clinical work performed so far. Potential advanced delivery strategies, which might improve the efficacy and adoption of intraperitoneal delivery of therapy for ovarian cancer, are also outlined.
卵巢癌是最致命的妇科恶性肿瘤,全球五年生存率为30%-50%。一线治疗包括细胞减灭术以及给予铂类小分子药物和紫杉醇。这些疗法传统上是通过静脉输注给药,不过也对腹腔给药进行了研究。卵巢癌腹腔给药的初步临床试验表明,与静脉给药相比,总体生存率有显著提高,但并非所有研究的结果都一致。最近,基于细胞的免疫疗法在卵巢癌治疗中受到关注。基于细胞的免疫疗法直接腹腔给药可能会促使局部免疫调节机制与所给予的免疫疗法协同发挥作用。基于这一理论,临床前研究已通过腹腔途径给予这些基于细胞的免疫疗法,并取得了有前景的结果。然而,基于细胞的免疫疗法腹腔给药的成功以及该技术的临床应用将取决于克服腹腔给药的挑战,并找到剂量、治疗方法和给药途径的最佳组合。我们综述了卵巢癌基于细胞的免疫疗法腹腔给药的潜在优缺点,以及迄今为止开展的临床前和临床研究工作。还概述了可能提高卵巢癌腹腔给药治疗效果和应用的潜在先进给药策略。