Cancer Vaccines in the Treatment of CML

描述（由申请方提供）：CML被认为是一种免疫应答性疾病，这是基于用同种异体T细胞治愈疾病的能力以及在对干扰素-α有应答的患者中对CML相关抗原的宿主免疫应答的证明。使用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相对无毒的细胞减少疗法，尽管完全的分子缓解仍然罕见。我们建议接种CML患者谁是在一个完全的血液学缓解，但有持续的细胞遗传学或分子证据的疾病，与一种新的同种异体肿瘤细胞为基础的疫苗，表达许多抗原显示存在于CML细胞和T细胞反应已被证明。本研究的两个主要目的是证明在甲磺酸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细胞应答的能力，并检验通过bcr/abl转录物的定量RT-PCR测定的此类应答将导致肿瘤负荷可测量的降低（或其消除）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.