Klammer M, Waterfall M, Samuel K, Turner M L, Roddie P H
University of Edinburgh-Leukaemia Research Fund, John Hughes Bennett Laboratory, Western General Hospital, Edinburgh EH4 2XU, UK.
Br J Haematol. 2005 May;129(3):340-9. doi: 10.1111/j.1365-2141.2005.05477.x.
We assessed the potential of tumour cell/dendritic cell fusion hybrids to generate in vitro anti-leukaemic T-cell responses following co-culture with autologous remission lymphocytes in six patients with acute myeloid leukaemia (AML). Comparison was made to anti-leukaemic responses induced by mature dendritic cells (mDC) co-cultured with autologous, irradiated myeloid blasts. Fusion hybrids induced anti-leukaemic T-cell immune responses in three of six patients. Tumour-pulsed mDC induced T-cellular responses in two other patients. Only one of six patients remission lymphocytes failed to develop leukaemia-directed immune responses following stimulation with either construct. Anti-proliferative properties of fusion hybrids against allogeneic lymphocytes were observed in mixed lymphocyte-leukaemia reactions and were found not to be specific to the cell fusion partners and did not prevent the ability of AML-mDC heterokaryons to induce autologous anti-leukaemic cytotoxicity. We conclude that tumour cell/dendritic cell fusion hybrids hold promise as a cellular vaccine for AML.
我们评估了肿瘤细胞/树突状细胞融合杂交体与6例急性髓系白血病(AML)患者的自体缓解期淋巴细胞共培养后在体外产生抗白血病T细胞反应的潜力。将其与成熟树突状细胞(mDC)与自体照射髓系母细胞共培养诱导的抗白血病反应进行了比较。融合杂交体在6例患者中的3例中诱导了抗白血病T细胞免疫反应。肿瘤脉冲mDC在另外2例患者中诱导了T细胞反应。6例患者中只有1例缓解期淋巴细胞在用任何一种构建体刺激后未能产生针对白血病的免疫反应。在混合淋巴细胞白血病反应中观察到融合杂交体对同种异体淋巴细胞的抗增殖特性,发现其并非细胞融合伙伴所特有,并且不影响AML-mDC异核体诱导自体抗白血病细胞毒性的能力。我们得出结论,肿瘤细胞/树突状细胞融合杂交体有望成为AML的细胞疫苗。