IMMUNIZATION WITH BEC2 ANTIID VACCINE AND GD3-LACTONE

描述：(申请者摘要)该项目的总体目标是 开发一种诱导高滴度免疫球蛋白抗体的免疫方法 抗黑色素瘤患者的GD3神经节苷脂。GD3是一个有吸引力的目标 对于免疫治疗，因为它在几乎所有的黑色素瘤上都有表达，它是 在极少的正常组织中表达，以及抗 GD3，如R24，可以在动物和小鼠体内诱导抗黑色素瘤作用 病人。之前为患者接种GD3疫苗的尝试已经完成 使用以下任一方法部分成功：a)GD3-内酯偶联到锁孔 并与佐剂QS21(GD3-内酯-KLH+QS21)混合或 B)BEC2抗独特型单抗与卡介苗混合。使用以下任一选项 这些疫苗可以在一个亚群中诱导出针对GD3的低滴度抗体 病人的数量。在本申请中，申请人建议测试 假设给患者接种一种形式的疫苗之后 用另一种形式的疫苗免疫将在诱导方面更好 抗GD3抗体与任何一种形式的疫苗相比，将单独诱导 GD3的高效价免疫球蛋白。具体目标1是进行临床试验 24例手术后无病的黑色素瘤患者 手术切除，但复发风险高的患者。他们将被随机化 接种BEC2+卡介苗一个疗程，然后再接种 GD3-内酯-K1H+QS21或GD3-内酯-K1H+QS21+BEC2+卡介苗。这个 申请人将评估和比较在中国诱导的抗GD3抗体反应 每只手臂，无论是数量上还是质量上，在免疫后 接种疫苗后进行第二个疗程的疫苗接种。次要的 该项目的目标是初步尝试识别T细胞， 确认GD3神经节苷脂。最近的几份出版物表明， 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。在特定目标2下，申请者将测试 患者外周血中的T细胞免疫后观察T细胞 对阵GD3。T细胞的反应性将通过两种方法进行评估 实验和Elispot。这样的T细胞有可能发挥重要作用 在辅助免疫治疗试验中观察到的低复发率的作用 之前使用的是BEC2。

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.