Cancer Vaccines in the Treatment of CML

描述(申请人提供)：慢性粒细胞白血病被认为是一种免疫反应性疾病，基于同种异体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。我们建议用一种新的基于同种异体肿瘤细胞的疫苗来接种血液学完全缓解但有持续细胞遗传学或分子疾病证据的CML患者，该疫苗表达CML细胞中存在的许多抗原，并已证明T细胞对这些抗原有反应。这项研究的两个主要目标将是证明在甲磺酸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)可衡量的减少(或消除)的假设。

DESCRIPTION (provided by applicant): CML is thought to be 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. We propose to vaccinate CML patients who are in a complete hematologic remission, but have persistent cytogenetic 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 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 Mesylate, 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.