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: 7943943
• 负责人: Jedd D. Wolchok
• 金额: $ 94.56万
• 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 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943943
• 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; Refractory; Reproduction spores; Research Personnel; Sampling; Serum; Site; Specimen; Staging; Surveys; T cell response; 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; randomized trial; 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）：现在非常清楚，用CTLA-4阻断抗体治疗的转移性黑色素瘤患者亚群具有持久的临床益处。我们小组和其他人的经验使我们有几个重要的问题需要回答，以便更多的病人受益。初步数据显示，对NY-ESO-1已有或诱导免疫的患者有更高的临床获益可能性。在大量接受辅助治疗的随机试验患者中验证这一观察结果，将进一步告诉我们NY-ESO-1免疫的重要性。如果我们最初的观察结果得到证实，这一知识可能会导致两个有影响的举措：(1)前瞻性地识别预先存在抗体的患者，并使用该免疫疗法和其他免疫疗法进行前期治疗；(2)将NY-ESO-1疫苗纳入无预先存在免疫的患者的治疗方案。在免疫治疗领域之外，这项研究将是对III期至IV期患者NY-ESO-1免疫的最大调查。血清状态在辅助治疗中的预后重要性将由我们的工作决定。此外，随着ipilimumab和其他免疫疗法走向标准使用，对ipilimumab单独或联合化疗治疗的患者进行分析将非常重要。了解化疗如何增强或削弱CTLA-4阻断剂的免疫作用将为合理的联合治疗提供信息。