CLINICAL TRIAL OF ANTIID VACCINE FOR NEUROBLASTOMA

描述：（申请人的摘要）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 出现了晚期疾病 对于先进的长期生存 婴儿期后的阶段仍然很差，尽管积极的治疗，包括骨 骨髓移植 迫切需要替代治疗方法。 在这一应用中，申请人计划探索积极的作用， 用抗Id疫苗Mab 1A 7直接抗GD 2的免疫疗法， 神经母细胞瘤 选择GD 2抗原作为免疫治疗的靶点， 基于申请人和其他人使用 抗GD 2单克隆抗体用于神经母细胞瘤的被动免疫治疗。 临床前 Mab 1A 7的研究证明了抗肿瘤抗体的产生 在同系小鼠、兔和食蟹猴中的反应。 初步 来自Mab 1A 7与佐剂混合的正在进行的I期试验的结果 QS-21在黑色素瘤患者中的应用表明， 耐受性好，可诱导免疫应答。 因此，申请人提出， 使用Mab 1A 7 + QS 21作为肿瘤疫苗进行初步研究， 晚期神经母细胞瘤的治疗。 此外，申请人计划 探索GM-CSF作为抗Id肿瘤辅助治疗的应用 疫苗 具体目标如下：1）评估 对抗Id疫苗+/- GM-CSF的免疫应答。 体液和 将测定细胞介导的免疫应答。 2)评价 抗Id疫苗治疗+/- GM-CSF的毒性。 3)来描述 抗Id疫苗+/- GM-CSF治疗晚期白血病的临床疗效观察 神经母细胞瘤及其与免疫反应的相关性。 这些承诺 应产生关于基于抗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应答的有效性。 它还应提供关于这种药物的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，并阐明了这种方法的治疗潜力， 其他GD 2（+）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.