Delluc Stéphanie, Tourneur Léa, Michallet Anne-Sophie, Boix Charlotte, Varet Bruno, Fradelizi Didier, Guillet Jean-Gérard, Buzyn Agnès
Département d'Immunologie, Institut Cochin, Institut National de la Santé Et de la Recherche Médicale U 567, Centre National de Recherche Scientifique (CNRS) UMR 8104, Université René Descartes, Paris V.
Haematologica. 2005 Aug;90(8):1050-62.
The poor prognosis of acute myeloid leukemia (AML) treated with conventional chemotherapy justifies seeking additional immunotherapeutic approaches to eliminate minimal residual disease. Hence, we evaluated the feasibility of generating in vitro antileukemic immune responses, which would bypass the need for epitope identification and rely on antigen presentation by autologous dendritic cells.
Naturally processed peptides were extracted by acid elution from circulating AML cells of six patients at diagnosis. Mature dendritic cells (mDC) were derived from autologous monocytes obtained when the patients were in complete remission, and were loaded with the pool of eluted peptides to stimulate autologous T lymphocytes in vitro.
We were able to induce in vitro antileukemic Th1 responses characterized by CD4(+) T-cell proliferation, significant interferon-gamma secretion by both CD4+ and CD8(+) T lymphocytes by recognition of autologous AML cells and generation of cytotoxic CD8(+) T lymphocytes.
These results demonstrate that naturally processed peptides eluted from AML cells and presented by differentiated autologous mDC could be immunogenic in vitro. Although more in vitro data will be needed to check the safety of such an approach, notably to rule out possible autoimmune adverse effects, these results lay the basis for a potentially effective antileukemic immunotherapy for high-risk AML patients with minimal residual disease.
采用传统化疗治疗急性髓系白血病（AML）预后较差，因此有必要寻求其他免疫治疗方法来清除微小残留病。因此，我们评估了体外产生抗白血病免疫反应的可行性，这种方法无需确定表位，而是依赖自体树突状细胞进行抗原呈递。
通过酸洗脱从6例AML患者诊断时的循环白血病细胞中提取天然加工的肽。成熟树突状细胞（mDC）来自患者完全缓解时获得的自体单核细胞，用洗脱肽库负载，以在体外刺激自体T淋巴细胞。
我们能够在体外诱导抗白血病Th1反应，其特征为CD4(+) T细胞增殖、CD4+和CD8(+) T淋巴细胞通过识别自体AML细胞分泌大量干扰素-γ以及产生细胞毒性CD8(+) T淋巴细胞。
这些结果表明，从AML细胞洗脱并由分化的自体mDC呈递的天然加工肽在体外具有免疫原性。尽管需要更多体外数据来检验这种方法的安全性，尤其是排除可能的自身免疫不良反应，但这些结果为针对具有微小残留病的高危AML患者进行潜在有效的抗白血病免疫治疗奠定了基础。
