Defining the Importance of Immunity to NY-ESO-1 in Melanoma Therapy and Prognosis

描述（由申请人提供）：现在很清楚，用CTLA-4阻断抗体治疗的转移性黑色素瘤患者亚组具有持久的临床获益。我们小组和其他人的经验使我们提出了几个需要回答的重要问题，以便更多的病人受益。初步数据显示，对NY-ESO-1具有预先存在或诱导的免疫力的患者具有更高的临床获益可能性。在一项随机试验中接受辅助治疗的大量患者中验证这一观察结果将进一步告知我们NY-ESO-1免疫的重要性。如果我们的初步观察得到证实，这一知识可能会导致两个有影响力的举措：（1）前瞻性地识别具有预先存在抗体的患者，以进行这种和其他免疫疗法的前期治疗;（2）将NY-ESO-1疫苗纳入没有预先存在免疫力的患者的治疗计划。在免疫治疗领域之外，这项研究将是对III期至IV期过渡期患者的NY-ESO-1免疫力的最大调查。我们的工作将确定血清状态在辅助治疗中的预后重要性。此外，对单独使用伊匹单抗或与化疗联合治疗的患者进行的拟议分析将非常重要，因为这种和其他免疫治疗药物正在走向标准使用。了解化疗如何增强或削弱CTLA-4阻断的免疫学作用将为合理的联合治疗提供信息。 公共卫生相关性：初步数据显示，对NY-ESO-1具有预先存在或诱导的免疫力的患者具有更高的临床获益可能性。在一项随机试验中接受辅助治疗的大量患者中验证这一观察结果将进一步告知我们NY-ESO-1免疫的重要性。

DESCRIPTION (provided by applicant): It is now quite clear that a subset of patients with metastatic melanoma treated with CTLA-4 blocking antibodies have durable clinical benefit. The experience of our group and others leads us to several vital questions which require answers so that more patients may benefit. The preliminary data show that patients with pre-existing or induced immunity to NY-ESO-1 have a higher likelihood of clinical benefit. Validation of this observation in the large population of patients treated on a randomized trial in the adjuvant setting will further inform us of the importance of NY-ESO-1 immunity. If our initial observations are confirmed, that knowledge could lead to two impactful moves: (1) prospective identification of patients with pre-existing antibodies for up-front treatment with this and other immunotherapies and (2) incorporation of NY-ESO-1 vaccines into treatment programs for patients with no pre-existing immunity. Outside of the area of immunotherapy, this study will be the largest survey of NY-ESO-1 immunity in patients at the stage III to IV transition. The prognostic importance of sero-status in the adjuvant setting will be determined by our work. Further, the proposed analysis of patients treated with ipilimumab alone or in combination with chemotherapy will be highly significant as this and other immunotherapeutics move toward standard use. Knowledge of how chemotherapy may augment or detract from the immunologic effects of CTLA-4 blockade will inform the field concerning rational combination therapies. PUBLIC HEALTH RELEVANCE: Preliminary data show that patients with pre-existing or induced immunity to NY-ESO-1 have a higher likelihood of clinical benefit. Validation of this observation in the large population of patients treated on a randomized trial in the adjuvant setting will further inform us of the importance of NY-ESO-1 immunity.