P1 - COMBINATION ACTIVATED T-CELL AND VACCINE THERAPY IN MYELOMA

我们的团队在开发和验证诱导方法方面取得了重大进展 恶性血液病患者的免疫功能。此应用程序的一个中心假设是多个 为了实现血液病的长期控制，需要进行生物和免疫操作。 恶性肿瘤；类似于发现联合化疗已被要求显著 改善大多数肿瘤的SUN/IVAL。我们已经开发出一种名为ID KLH的候选疫苗，它针对的是 由骨髓瘤细胞产生的患者特有的和肿瘤特有的M蛋白。这种疫苗，作为一种 单一药物，已被证明在第二阶段和第111阶段试验中具有安全性和临床活性 滤泡性淋巴瘤。作为对疫苗研究的赞扬，我们最近在受试者中进行的随机L/11期研究 晚期骨髓瘤患者显示疫苗预置T细胞过继免疫治疗可导致 鼓励大剂量化疗和自体造血后的免疫重建 干细胞移植(SCT)。此外，我们首次在人类身上提供了领养的证据 免疫疗法联合疫苗接种可在数周内产生保护性免疫。 在SCT之后。基于这些有希望的临床结果，以及该临床试验的安全性和可行性 现在，我们提出了一系列临床试验，以诱导骨髓瘤患者的肿瘤特异性免疫。 为了在我们共同取得进展的基础上再接再厉，以下两个具体目标将检验疫苗可以 与骨髓瘤患者的过继免疫治疗相结合，目标是产生 分子靶向和有效的抗肿瘤免疫： 具体目的1.进行II期临床试验，研究其可行性和免疫原性 晚期肺癌患者移植后效应性T细胞重建及独特型-KLH型疫苗接种 骨髓瘤。获得完全的监管许可才能打开该方案，并进行临床试验。该协议 将在MD安德森癌症中心和宾夕法尼亚大学开放，并关闭 入选时-60名患者入选。 具体目标2.确定联合免疫疗法是否会增加骨髓瘤 增强免疫力，减轻肿瘤负担。我们将测定(A)细胞免疫和(B)体液免疫 回答和(C)了解这是否与所有患者的副蛋白减少程度相关 不管他们是否接种了疫苗，然后只在疫苗接受者中。基座 根据我们的初步数据，我们预计ID特异性免疫力和 副蛋白水平。

Our team has made significant progress in our efforts to develop and validate methods to induce immunity in patients with hematologic malignancies. A central hypothesis of this application is that multiple biologic and immunologic maneuvers will be required in order to achieve long-term control of hematologic malignancies; similar to the finding that combination chemotherapy has been required to significantly improve sun/ival in most tumors. We have developed a candidate vaccine termed Id KLH, that targets the patient specific and tumor specific M-protein that is produced by myeloma cells. This vaccine, given as a single agent, has been demonstrated to have safety and clinical activity in phase II and phase 111 trials in follicular lymphoma. Complimenting the vaccine studies, our recent randomized phase l/ll studies in subjects with advanced myeloma showed adoptive immunotherapy with vaccine primed T cells resulted in an encouraging immunologic reconstitution following high dose chemotherapy and autologous hematopoietic stem cell transplantation (SCT). Furthermore, we provided the first evidence in humans that adoptive mmunotherapy combined with vaccinafion could result in the generation of protective immunity within weeks following the SCT. Based on these promising clinical results, and on the safety and feasibility of this clinical trial, we now propose a series of clinical trials to induce tumor-specific immunity in pafients with myeloma. To build on our combined progress, the following two specific aims will test the hypothesis that vaccines can be combined with adoptive immunotherapy in patients with myeloma with the goal of generating a moleculariy targeted and potent antitumor immunity: ¿ Specific Aim 1. Conduct a phase II clinical trial to study the feasibility and immunogenicity of post-transplant effector T cell reconstitution and Idiotype-KLH vaccination in patients with advanced myeloma. Obtain full regulatory clearance to open the protocol, and conduct the clinical trial. The protocol will be opened at the MD Anderson Cancer Center and the University of Pennsylvania, and closed to enrollment when -60 patients are enrolled. ¿ Specific Aim 2. Determine whether the combination immunotherapy regimen augments myeloma immunity and decreases tumor burdens. We will determine (a) cellular and (b) humoral immune responses and (c) learn whether this correlates with the degree of paraprotein reduction for all patients regardless of whether they received the vaccine or not and then amongst vaccine recipients alone. Based upon our preliminary data, we expect to see a trend between Id-specific immunity and a reduction of paraprotein levels.