IMMUNIZATION WITH BEC2 ANTIID VACCINE AND GD3-LACTONE

描述：（申请人摘要）本项目的总体目标是 开发诱导高滴度IgG抗体的免疫方法 GD 3神经节苷脂治疗黑色素瘤 GD 3是一个有吸引力的目标 对于免疫治疗，因为它几乎在所有黑色素瘤上表达， 在少数正常组织中表达，针对 GD 3，如R24，可以在动物和哺乳动物中诱导抗黑色素瘤作用。 患者 以前尝试免疫患者对抗GD 3， 使用以下任一种方法部分成功：a）GD 3-内酯缀合至锁孔 血蓝蛋白并与佐剂QS 21（GD 3-内酯-KLH + QS 21）混合，或 B）与佐剂BCG混合的BEC 2抗独特型MA B。 使用任何一种 在这些疫苗中，可以在亚组中诱导针对GD 3的低滴度抗体， 病人。 在本申请中，申请人建议测试 假设用一种形式的疫苗引发患者， 用另一种形式的疫苗免疫在诱导 与单独的任一种形式的疫苗相比，抗GD 3抗体将诱导 抗GD 3高滴度IgG。 具体目标1：开展临床试验 涉及24名手术后无病的黑色素瘤患者， 切除但复发风险高的患者。 他们将被随机分组 接种BEC 2 + BCG，然后接种 GD 3-内酯-KLH + QS 21，或GD 3-内酯-KLH + QS 21，然后是BEC 2 +BCG。 的 申请人将评估并比较在 在用免疫后，每组定量和定性地， “初免”疫苗和第二个接种疗程后。 次级 该项目的目标是初步尝试识别T细胞， 识别GD 3神经节苷脂。 最近的一些出版物表明， 在某些情况下，T细胞可以识别碳水化合物和其他 非蛋白质分子 根据具体目标2，申请人将测试 从患者外周血T细胞免疫来看T细胞 针对GD 3。 T细胞反应性将使用增殖和免疫组织化学评估。 测定和通过ELISPOT。 这种T细胞可能在免疫系统中起着重要的作用。 在辅助免疫治疗试验中观察到的低复发率中的作用 以前使用BEC 2。

DESCRIPTION: (Applicant's Abstract) The overall goal of this project is to develop a method of immunization that induces high titer IgG antibodies against GD3 ganglioside in melanoma patients. GD3 is an attractive target for immunotherapy because it is expressed on virtually all melanoma, it is expressed on few normal tissues, and monoclonal antibodies (MAb) against GD3, such as R24, can induce anti-melanoma effects in animals and in patients. Previous attempts to immunize patients against GD3 have been partially successful using either: a) GD3-lactone conjugated to keyhole limpet hemocyanin and mixed with the adjuvant QS21 (GD3-lactone-KLH+QS21) or b) BEC2 anti-idiotypic MAb mixed with the adjuvant BCG. Using either of these vaccines, low titer antibodies against GD3 can be induced in a subset of patients. In this application, the applicant proposes to test the hypothesis that priming patients with one form of vaccine followed by immunization with the other form of vaccine will be superior in inducing anti-GD3 antibodies compared to either form of vaccine alone and will induce high titer IgG against GD3. Specific Aim 1 is to conduct a clinical trial involving 24 melanoma patients who are free of disease after surgical resection but who are at high risk for recurrence. They will be randomized to be immunized either with a course of BEC2 + BCG followed by GD3-lactone-KLH+QS21, or GD3-lactone-KLH+QS21 followed by BEC2+BCG. The applicant will assess and compare the anti-GD3 antibody response induced in each arm, both quantitatively and qualitatively, after immunization with the "priming" vaccine and after the second course of vaccination. A secondary goal of this project is to make an initial attempt to identify T cells that recognize GD3 ganglioside. Several recent publications have indicated that, in some circumstances, T cells can recognize carbohydrates and other non-protein molecules. Under Specific Aim 2, the applicant will test peripheral blood T cells from the patients immunized to look at T cells against GD3. T cell reactivity will be assessed using both a proliferation assay and by ELISPOT. It is possible that such T cells play an important role in the low recurrence rates observed in adjuvant immunotherapy trials previously conducted using BEC2.