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

定义 NY-ESO-1 免疫在黑色素瘤治疗和预后中的重要性

• 批准号: 7853506
• 负责人: Jedd D. Wolchok
• 金额: $ 91.87万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7853506
• 关键词: Adjuvant; Adjuvant Therapy; Affect; Antibodies; Antibody Formation; Antigens; Area; Biological Markers; Blocking Antibodies; Blood specimen; CD8B1 gene; CTAG1 gene; Cancer Center; Cancer Patient; Carboplatin; Center Core Grants; Clinical; Combined Modality Therapy; Dacarbazine; Data; Disease; Funding; Goals; Grant; Immune response; Immunity; Immunologic Monitoring; Immunologics; Immunology procedure; Immunotherapeutic agent; Immunotherapy; Institutes; Knowledge; Lead; Literature; Malignant neoplasm of ovary; Malignant neoplasm of testis; Measures; Memorial Sloan-Kettering Cancer Center; Metastatic Melanoma; Monitor; Monoclonal Antibodies; Paclitaxel; Patients; Placebos; Prevalence; Process; Prostate; Qualifying; Randomized Controlled Clinical Trials; Refractory; Reproduction spores; Research Personnel; Sampling; Serum; Site; Specimen; Staging; Surveys; T-Lymphocyte; Time; United States National Institutes of Health; Vaccines; Validation; Work; anticancer research; base; chemotherapy; cohort; experience; melanoma; outcome forecast; patient population; peripheral blood; prognostic; prospective; public health relevance; response; treatment program

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.

描述（由申请人提供）：现在很明显，用CTLA-4阻断抗体治疗的转移性黑色素瘤患者子集具有持久的临床益处。我们小组和其他人的经验使我们提出了一些需要答案的重要问题，以便更多的患者受益。初步数据表明，对NY-ESO-1的免疫力有免疫力的患者具有更高的临床益处。在佐剂环境中随机试验中接受的大量患者对这一观察结果的验证将进一步告知我们NY-ESO-1免疫的重要性。如果我们的最初观察结果得到证实，那么知识可能会导致两种影响力的动作：（1）预先鉴定患有这种和其他免疫疗法的预先治疗的抗体患者，以及（2）将NY-ESO-1疫苗纳入没有预先存在免疫力的患者中。在免疫疗法领域之外，这项研究将是III期至IV期转变患者的NY-ESO-1免疫的最大调查。血清状态在辅助环境中的预后重要性将取决于我们的工作。此外，由于这种和其他免疫治疗剂朝着标准使用迈进，因此对单独或与化学疗法结合治疗的患者进行了对患者的建议分析。了解化学疗法如何增加或减损CTLA-4封锁的免疫作用，将为领域提供有关理性组合疗法的信息。 公共卫生相关性：初步数据表明，对NY-ESO-1的免疫力或诱导免疫力的患者具有更高的临床益处。在佐剂环境中随机试验中接受的大量患者对这一观察结果的验证将进一步告知我们NY-ESO-1免疫的重要性。