Moviglia Gustavo A, Carrizo Antonio G, Varela Gabriela, Gaeta Carlos A, Paes de Lima Andrea, Farina Pablo, Molina Hugo
Fundación Regina Mater, Buenos Aires, Argentina.
Hematol Oncol Stem Cell Ther. 2008 Jan-Mar;1(1):3-13. doi: 10.1016/s1658-3876(08)50054-9.
Glioblastoma multiforme (GBM), the most aggressive glioma, presents with a rapid evolution and relapse within the first year, which is attributed to the persistence of tumor stem cells (TSC) and the escape of immune surveillance. Mixed leukocyte culture (MLC) cytoimplant has been shown to function as a powerful intratumor pro-inflammatory cytokine pump. Tumor B-cell hybridoma (TBH) vaccines have been shown to function as antigen-presenting cells. We evaluated the toxicity and efficiency of each treatment alone and in combination.
In an open study, 12 consecutive patients were evenly divided into 3 groups, each group receiving 3 different treatments. Patients in Group 1 were treated, after diagnosis, with debulking surgery (DS)+radiotherapy (Rx), and after the first relapse underwent DS+MLC treatment. Patients in Group 2 were similarly treated but after the first relapse underwent DS+MLC+TBH. Finally, patients in Group 3 were similarly treated but after the first relapse underwent DS+TBH. Nestin PAP stain assessed TSC participation in TBH.
Treatment with MLC had strong and rapid therapeutic effects, but was limited in duration and induced various degrees of brain inflammation. Treatment with MLC+TBH acted synergistically, provoking a rapid, strong and lasting therapeutic response but also generating different degrees of brain inflammation. A lasting therapeutic effect without generating high degrees of brain inflammation occurred in patients treated with TBH vaccine alone.
TSC vaccine consisting of TBH alone seems to have potent adjuvant reactions overcoming both persistence of tumor stem cells and immune escape of GBM without provoking an encephalitic reaction.
多形性胶质母细胞瘤（GBM）是最具侵袭性的胶质瘤，在第一年就会迅速进展和复发，这归因于肿瘤干细胞（TSC）的持续存在和免疫监视的逃逸。混合白细胞培养（MLC）细胞植入物已被证明可作为强大的肿瘤内促炎细胞因子泵发挥作用。肿瘤B细胞杂交瘤（TBH）疫苗已被证明可作为抗原呈递细胞发挥作用。我们评估了每种治疗单独及联合使用时的毒性和疗效。
在一项开放性研究中，12例连续患者被平均分为3组，每组接受3种不同治疗。第1组患者在诊断后接受减瘤手术（DS）+放疗（Rx），首次复发后接受DS+MLC治疗。第2组患者接受类似治疗，但首次复发后接受DS+MLC+TBH治疗。最后，第3组患者接受类似治疗，但首次复发后接受DS+TBH治疗。巢蛋白PAP染色评估TSC在TBH中的参与情况。
MLC治疗具有强烈且迅速的治疗效果，但持续时间有限，并诱发了不同程度的脑部炎症。MLC+TBH联合治疗具有协同作用，引发了快速、强烈且持久的治疗反应，但也产生了不同程度的脑部炎症。单独使用TBH疫苗治疗的患者出现了持久的治疗效果且未引发高度的脑部炎症。
单独由TBH组成的TSC疫苗似乎具有强大的佐剂反应，既能克服肿瘤干细胞的持续存在，又能克服GBM的免疫逃逸，且不会引发脑炎反应。
