K562/GM-CSF VACCINATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。CML被认为是一种免疫应答性疾病，基于同种异体T细胞治愈疾病的能力，以及在对干扰素- α有反应的患者中对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获得的显著临床反应提供了一种相对无毒的细胞减少治疗，尽管完全的分子缓解仍然很少。在这项研究中，我们正在为血液学完全缓解，但有持续细胞遗传学或分子证据的CML患者接种一种新型异体肿瘤细胞疫苗，该疫苗表达CML细胞中存在的许多抗原，并已证明T细胞对其有反应。该疫苗与Toll样受体9（咪喹莫特）的局部激动剂联合施用。本研究的两个主要目标将是证明在伊马替尼缓解期接种疫苗的患者中产生和增强CML特异性T细胞反应的能力，以及通过bcr/abl转录物的定量RT-PCR检测这种反应将导致可测量的肿瘤负担减少（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.