CLINICAL TRIAL OF ANTIID VACCINE FOR NEUROBLASTOMA

神经母细胞瘤抗疫苗的临床试验

• 批准号: 2896645
• 负责人: Alice L. Yu
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2896645
• 关键词: T lymphocyte; antiidiotype antibody; antitumor antibody; cell proliferation; cellular immunity; clinical research; clinical trials; colony stimulating factor; cytokine; cytotoxicity; drug screening /evaluation; enzyme linked immunosorbent assay; human subject; human therapy evaluation; humoral immunity; immune tolerance /unresponsiveness; immunization; monoclonal antibody; neoplasm /cancer classification /staging; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; neuroblastoma; pediatric neoplasm /cancer

DESCRIPTION: (Applicant's Abstract) Neuroblastoma is the most common extra-cranial solid tumor in children, with two thirds of patients presenting with advanced disease. The long-term survival for the advanced stages after infancy remains poor, despite aggressive therapy including bone marrow transplant. Alternative therapeutic approaches are urgently needed. In this application, the applicant plans to explore the role of active immunotherapy with an anti-Id vaccine, Mab 1A7, directed against anti-GD2 in neuroblastoma. The choice of GD2 antigen as the target of immunotherapy is based on the promising results obtained by the applicant and others using anti-GD2 Mabs for passive immunotherapy of neuroblastoma. Preclinical studies of Mab 1A7 demonstrated the generation of an antitumor antibody response in syngeneic mice, rabbits, and cynomolgus monkeys. Preliminary results from an ongoing phase I trial of Mab 1A7 mixed with the adjuvant QS-21 in melanoma patients have shown that such immunotherapy is well-tolerated and can induce immune response. Thus, the applicant proposes to conduct a pilot study using Mab 1A7 + QS21 as a tumor vaccine for treatment of advanced stage neuroblastoma. In addition, the applicant plans to explore the use of GM-CSF as an adjuvant for anti-Id based cancer vaccine. The specific aims are as follows: 1) To assess the frequency of immune responses to the anti-Id vaccine +/- GM-CSF. Both humoral and cell-mediated immune responses will be determined. 2) To evaluate the toxicities of anti-Id vaccine therapy +/- GM-CSF. 3) To describe the clinical efficacy of anti-Id vaccine therapy +/- GM-CSF in advanced stage neuroblastoma and the correlation with immune responses. These undertakings should yield useful information on the safety of the anti-Id based tumor vaccine and its effectiveness in inducing immune response in neuroblastoma. It should also provide preliminary data on the clinical efficacy of such vaccine and the potential of GM-CSF as an adjuvant for anti-Id based tumor vaccine and shed light on the therapeutic potential of such an approach in other GD2(+) tumors, such as small cell lung cancer, melanoma and some sarcomas.

描述：（申请人摘要）神经母细胞瘤是最常见的 儿童颅外实体瘤，三分之二的患者 表现为晚期疾病。 先进者的长期生存 尽管进行了包括骨治疗在内的积极治疗，但婴儿期后的阶段仍然很差 骨髓移植。 迫切需要替代治疗方法。 在本申请中，申请人计划探索主动的作用 使用抗Id疫苗Mab 1A7进行免疫治疗，针对抗GD2 成神经细胞瘤。 选择GD2抗原作为免疫治疗的靶点是 基于申请人和其他人使用所获得的有希望的结果 用于神经母细胞瘤被动免疫治疗的抗 GD2 Mab。 临床前 Mab 1A7 的研究证明了抗肿瘤抗体的产生 同基因小鼠、兔子和食蟹猴的反应。 初步的 来自正在进行的 Mab 1A7 与佐剂混合的 I 期试验的结果 QS-21 在黑色素瘤患者中的应用表明，这种免疫疗法是有效的 耐受性良好，可诱导免疫反应。 因此，申请人建议 使用 Mab 1A7 + QS21 作为肿瘤疫苗进行试点研究 晚期神经母细胞瘤的治疗。 此外，申请人计划 探索使用 GM-CSF 作为抗 Id 癌症的佐剂 疫苗。 具体目标如下： 1）评估频率 对抗 Id 疫苗的免疫反应 +/- GM-CSF。 既幽默又 细胞介导的免疫反应将被确定。 2) 评估 抗Id疫苗治疗的毒性+/- GM-CSF。 3）描述 晚期阶段抗Id疫苗治疗+/- GM-CSF的临床疗效 神经母细胞瘤及其与免疫反应的相关性。 这些事业 应该会产生关于基于抗 Id 的肿瘤的安全性的有用信息 疫苗及其在神经母细胞瘤中诱导免疫反应的有效性。 它还应提供此类药物临床疗效的初步数据。 疫苗和 GM-CSF 作为抗 Id 肿瘤佐剂的潜力 疫苗并揭示了这种方法的治疗潜力 其他 GD2(+) 肿瘤，例如小细胞肺癌、黑色素瘤和一些 肉瘤。