Sabbatini Paul, Odunsi Kunle
Medical Gynecologic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
J Clin Oncol. 2007 Jul 10;25(20):2884-93. doi: 10.1200/JCO.2007.11.0775.
The clinical course of ovarian cancer is often marked by periods of relapse and remission until chemotherapy resistance develops. Patients in remission with minimal disease burdens are ideally suited for the evaluation of immune-based strategies. The role of immune surveillance in improving outcome has been supported by the correlation of increased survival with the presence or absence of tumor-infiltrating lymphocytes in a given patient. Major obstacles to the development of successful immune strategies include the identification of tumor-restricted immunogenic targets, generation of a sufficient immune response to cause tumor rejection, and approaches to overcome evasion of immune attack. As optimal strategies are being developed, many questions remain. Some of the questions are as follows: What is the best antigen form (eg, peptides, proteins, or tumor lysates)? What are the appropriate adjuvants? Are monovalent or multivalent vaccines likely to be more effective? What is the optimal frequency and duration of vaccination? How should antigen-specific responses be monitored? How should the anticancer response be maintained? In this review, we will explore representative examples of immune strategies under investigation for patients with ovarian carcinoma that illustrate many of these issues. We will review ongoing phase III studies for patients in first clinical remission. Basic principles generic to all these immunotherapeutic approaches will be discussed in the hopes of yielding the most promising results as the field continues to evolve.
卵巢癌的临床病程通常以复发和缓解期为特征,直至出现化疗耐药。疾病负担最小的缓解期患者非常适合评估基于免疫的策略。免疫监视在改善预后方面的作用已得到支持,即特定患者的生存时间延长与肿瘤浸润淋巴细胞的有无相关。成功的免疫策略发展的主要障碍包括识别肿瘤特异性免疫原性靶点、产生足以导致肿瘤排斥的免疫反应以及克服免疫攻击逃避的方法。随着最佳策略的不断发展,仍有许多问题存在。其中一些问题如下:最佳抗原形式是什么(例如,肽、蛋白质或肿瘤裂解物)?合适的佐剂有哪些?单价疫苗还是多价疫苗可能更有效?最佳接种频率和持续时间是多少?应如何监测抗原特异性反应?应如何维持抗癌反应?在本综述中,我们将探讨正在研究的针对卵巢癌患者的免疫策略的代表性例子,这些例子说明了其中许多问题。我们将回顾针对首次临床缓解期患者正在进行的III期研究。将讨论所有这些免疫治疗方法通用的基本原则,以期随着该领域的不断发展取得最有前景的结果。