Depletion of regulatory T cells by targeting folate receptor 4 enhances the potency of a GM-CSF-secreting tumor cell immunotherapy
Depletion of regulatory T cells by targeting folate receptor 4 enhances the potency of a GM-CSF-secreting tumor cell immunotherapy
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DOI：
10.1016/j.clim.2013.05.011
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发表时间：
2013-08-01
影响因子：
8.6
通讯作者：
Jooss, Karin
中科院分区：
文献类型：
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作者：
Liang, Spencer C.;Moskalenko, Marina;Jooss, Karin
在这篇报道中，Treg耗竭性抗FR 4抗体与分泌GM-CSF的肿瘤细胞免疫疗法（GVAX）组合用于治疗荷黑色素瘤动物。用GVAX治疗的动物的中位存活时间（MST）为41天，相比之下，未治疗的动物的MST为32天。抗FR 4单药治疗对MST无影响。抗FR 4和GVAX的组合显著延长MST至55天，表明这两种试剂可以协同作用。联合治疗增加了CD 8 T细胞的IFN-γ和颗粒酶B的表达。与抗CD 25介导的Treg耗竭相反，在GVAX后施用抗FR 4不降低功效，表明抗FR 4不耗竭由GVAX诱导的效应细胞。阻断性CTLA 4抗体与GVAX和抗FR 4的三重组合进一步提高了总体存活率并减少了良好建立的黑素瘤的生长。综合考虑，抗FR 4抗体和GVAX可能是治疗癌症患者的一种有前途的方法。(C)2013 Elsevier Inc. All rights reserved.
In this report, a Treg-depleting anti-FR4 antibody is combined with a GM-CSF-secreting tumor cell immunotherapy (GVAX) for treatment of melanoma-bearing animals. Median survival time (MST) of animals treated with GVAX was 41 days, compared to a MST of 32 days in untreated animals. Anti-FR4 monotherapy had no effect on MST. Combination of anti-FR4 and GVAX significantly prolonged MST to 55 days, suggesting that these two agents can function cooperatively. Combination therapy increased expression of IFN-gamma and granzyme B by CD8 T cells. In contrast to anti-CD25-mediated Treg depletion, administration of anti-FR4 after GVAX did not reduce efficacy, suggesting that anti-FR4 does not deplete effector cells induced by GVAX. Triple combination of a blocking CTLA4 antibody with GVAX and anti-FR4 further enhanced overall survival and reduced growth of well-established melanomas. Considered together, anti-FR4 antibody and GVAX may be a promising approach for the treatment of patients with cancer. (C) 2013 Elsevier Inc. All rights reserved.