Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer
Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer
复制标题
DOI：
10.1080/14653240701589221
复制
发表时间：
2007-01-01
期刊：
影响因子：
4.5
通讯作者：
Felzmann, T.
中科院分区：
文献类型：
--
作者：
Dohnal, A. M.;Witt, V.;Felzmann, T.
使用DC作为APC的肿瘤疫苗具有良好的耐受性，并在临床研究中显示出一定的疗效。IL-12是一种对1型辅助性T细胞(Th1)和细胞毒性T淋巴细胞(CTL)的分化至关重要的细胞因子，当从基于DC的肿瘤疫苗中释放出来时，可能会支持细胞T细胞反应的产生。方法我们采用了肿瘤细胞裂解物+锁孔斑点花青素(KLH)负载的肿瘤细胞裂解物和48h的脂多糖(LPS)+干扰素-γ刺激的完全成熟的DC，这些DC不会释放IL-12，8名患者皮下注射，最多6小时刺激半成熟(Sm)DC，这是产生IL-12的有力来源，结果应用IL-12释放的SMDC免疫后未见严重不良反应，延迟超敏反应(DTH)试验中多数患者对KLH呈阳性反应。此外，在DTH试验中，6名接受结内治疗的患者中有3名对肿瘤抗原有反应。讨论我们得出结论，以DC为基础的肿瘤疫苗能够释放免疫调节细胞因子IL-12，治疗是安全可行的，并有可能在儿童癌症患者中诱导细胞免疫反应。
BackgroundCancer vaccines employing DC in their capacity as APC have been tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response.MethodsWe applied tumor cell lysate plus keyhole limpet bemocyanin (KLH)-loaded and 48-h lipopolysaccharide (LPS) plus IFN-gamma-stimulated fully mature DC, which do not release IL-12, subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm) DC, which are potent producers of IL-12, subcutaneously (n = 6) or intranodally (n = 8) as a cancer vaccine to patients suffering from advancedsolid pediatric malignancies.ResultsNo serious adverse events were observed following application of IL-12-releasing smDC Following immunization the majority of patients responded positively to KLH in a delayed-type hypersensitiviy (DTH) test. In addition, three of six intranodally treated patients responded to the tumor Ag in the DTH test.DiscussionWe conclude that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in pediatric cancer patients.