CLINICAL TRIAL OF ANTIID VACCINE FOR NEUROBLASTOMA

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 出现晚期疾病。先进人才的长期生存 婴儿期以后的阶段仍然很差，尽管包括骨骼在内的积极治疗 骨髓移植。迫切需要替代的治疗方法。 在本申请中，申请者计划探索Active的角色 抗ID疫苗单抗1A7针对小鼠抗GD2的免疫治疗 神经母细胞瘤。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 抗GD2单抗用于神经母细胞瘤的被动免疫治疗。临床前 单抗1A7的研究证实了抗肿瘤抗体的产生 同基因小鼠、兔和食蟹猴的反应。初步 正在进行的单抗1A7与佐剂混合的I期试验结果 QS-21在黑色素瘤患者中的研究表明，这种免疫疗法是 耐受性好，可诱导免疫反应。因此，申请人提出了 用单抗1A7+QS21作为肿瘤疫苗的初步研究 晚期神经母细胞瘤的治疗。此外，申请人还计划 GM-CSF作为抗-ID基癌辅助治疗的探讨 疫苗。具体目标如下：1)评估 抗-ID疫苗+/-GM-CSF的免疫应答。无论是幽默的还是 将确定细胞介导的免疫反应。2)评估 抗-ID疫苗治疗+/-GM-CSF的毒性。3)描述 抗-ID疫苗+/-GM-CSF治疗晚期的临床疗效观察 神经母细胞瘤及其与免疫反应的相关性。这些承诺 应该提供关于基于抗ID的肿瘤的安全性的有用信息 疫苗及其诱导神经母细胞瘤免疫反应的有效性。 它还应该提供关于这种药物的临床疗效的初步数据 GM-CSF疫苗及其作为抗ID肿瘤佐剂的潜力 疫苗，并阐明了这种方法的治疗潜力 其他GD2(+)肿瘤，如小细胞肺癌、黑色素瘤和一些 肉瘤。

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.