CLINICAL TRIAL OF ANTIID VACCINE FOR NEUROBLASTOMA

神经母细胞瘤抗疫苗的临床试验

• 批准号: 2687536
• 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/2687536
• 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：（申请人的摘要）神经母细胞瘤是最常见的 儿童的颅外实体瘤，有三分之二的患者 出现晚期疾病。 高级的长期生存 婴儿后的阶段仍然很差，尽管侵略性疗法包括骨骼 骨髓移植。 迫切需要替代治疗方法。 在此应用程序中，申请人计划探索活跃的作用 抗ID疫苗的免疫疗法，MAB 1A7，针对抗GD2在 成神经细胞瘤。 选择GD2抗原作为免疫疗法的靶标的是 基于申请人和其他人使用的有希望的结果 抗GD2 mABS用于神经母细胞瘤的被动免疫疗法。 临床前 MAB 1A7的研究表明抗肿瘤抗体的产生 合成小鼠，兔子和cynomolgus猴子的反应。 初步的 MAB 1A7与佐剂混合的I阶段试验的结果 黑色素瘤患者的QS-21表明这种免疫疗法是 耐受耐受性，可以诱导免疫反应。 因此，申请人提出 使用MAB 1A7 + QS21作为肿瘤疫苗进行试验研究 治疗晚期神经母细胞瘤。 此外，申请人计划 探索使用GM-CSF作为抗ID癌症的辅助 疫苗。 具体目的如下：1）评估 对抗ID疫苗+/- GM-CSF的免疫反应。 两者都有体液和 将确定细胞介导的免疫反应。 2）评估 抗ID疫苗疗法的毒性+/- GM-CSF。 3）描述 晚期抗ID疫苗疗法的临床疗效+/- GM-CSF 神经母细胞瘤和免疫反应的相关性。 这些事业 应产生有关抗ID肿瘤安全性的有用信息 疫苗及其在神经母细胞瘤中诱导免疫反应的有效性。 它还应该提供有关此类临床功效的初步数据 疫苗和GM-CSF作为抗ID肿瘤佐剂的潜力 在这种方法中的治疗势 其他GD2（+）肿瘤，例如小细胞肺癌，黑色素瘤和一些 肉瘤。