Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma
Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma
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DOI：
10.1038/sj.gt.3303072
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发表时间：
2008-02-01
期刊：
影响因子：
5.1
通讯作者：
Glikin, G. C.
中科院分区：
文献类型：
--
作者：
Finocchiaro, L. M. E.;Glikin, G. C.
我们评估了手术辅助治疗犬恶性黑色素瘤的安全性、有效性和抗肿瘤效果。这种方法将自杀基因疗法与皮下疫苗结合起来，皮下疫苗由形成化的肿瘤细胞和辐照的产生人白细胞介素-2和粒细胞-巨噬细胞集落刺激因子的异种细胞组成。术后腔缘浸润脂质胸苷激酶自杀基因与更昔洛韦联合给药。所有患者毒性很小或没有毒性。相对于手术治疗的对照组（SC），这种联合治疗（CT）显著增加了局部无疾病的患者比例，从6%增加到58%，无远处转移的患者比例从43%增加到78% （Fisher’s Exact test）。此外，CT显着改善SC总78（23-540）和无转移生存112（0-467）天至1312天以上（各自范围：43-1312和0-1312）（Kaplan-Meier分析）。在接受部分手术或出现局部复发的患者中，49%的客观反应（平均85%的肿瘤肿块消失）证实了CT的有效性，而22%的患者显示肿瘤进展，94%的SC患者显示肿瘤进展。因此，手术辅助CT控制肿瘤生长，延缓或预防术后复发和远处转移，显著延长生存期，恢复生活质量。
We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.