VACCINATION IN COMBINATION WITH IMATINIB MESYLATE FOR CHRONIC MYELOID LEUKEMIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 向公众发布项目说明-03-08-12-05 CML被认为是一种免疫反应性疾病，其基础是用同种异体T细胞治愈疾病的能力，以及对干扰素-α有反应的患者对CML相关抗原的宿主免疫反应。选择性酪氨酸激酶抑制剂甲磺酸伊马替尼取得了显著的临床反应，提供了一种相对无毒的细胞还原疗法，尽管完全分子缓解仍然很少见。在这项研究中，我们正在用一种新型的基于同种异体肿瘤细胞的疫苗来接种CML患者，这些患者处于血液学完全缓解状态，但有持续的细胞遗传学或分子疾病证据，这种疫苗表达了CML细胞中存在的许多抗原，并证明了T细胞对这些抗原的反应。疫苗与Toll样受体9(咪喹莫特)的局部激动剂联合使用。这项研究的两个主要目标将是证明在伊马替尼缓解期间接种疫苗的患者产生和增强CML特异性T细胞反应的能力，并检验通过bcr/abl转录本的定量RT-PCR检测这种反应将导致肿瘤负担(或其消除)可测量的减少(或消除)的假设。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Description of Project for Release to Public- 03-08-12-05 CML is thought to an immunologically responsive disease based on the ability to cure the disease with allogeneic T cells as well as the demonstration of host immune responses to CML-associated antigens in patients who have responded to interferon-alpha. The dramatic clinical responses obtained with the selective tyrosine kinase inhibitor Imatinib Mesylate has provided a relatively non-toxic cytoreductive therapy, although complete molecular remissions remain rare. In this study, we are vaccinating CML patients who are in a complete hematologic remission, but have persistent cytogeneic or molecular evidence of disease, with a novel allogeneic tumor cell-based vaccine that expresses many of the antigens shown to be present in CML cells and to which T cell responses have been demonstrated. The vaccine is administered in conjunction with a topical agonist to Toll Like Receptor 9 (imiquimod). The two major objectives of this study will be to demonstrate the ability to generate and augment CML specific T cell responses in patients vaccinated while in remission on imatinib, and to test the hypothesis that such responses will lead to a measurable reduction in tumor burden (or its elimination) as assayed by quantitative RT-PCR of bcr/abl transcripts.