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首页> 外文期刊>Journal of immunotherapy >Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses.
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Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses.

机译:用白介素18和白介素12编码的质粒DNA进行的双盲安慰剂对照研究显示了灰马转移性黑色素瘤的抗肿瘤作用。

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摘要

Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmid DNA, interleukin-12-encoding plasmid DNA, or empty plasmid DNA (control group), injected intratumorally, respectively. Tumor response was assessed using ultrasound and caliper measurements and histologic assessment of tumor biopsies. Significant tumor regression could be shown in both the treatment groups receiving IL-18 and IL-12-encoding plasmid DNA whereas placebo-treated control patients showed tumor growth over the course of the treatment. In addition, 7 of 10 tumors from horses treated with IL-18 or IL-12 showed peritumoral and/or intratumoral inflammatory infiltrates after treatment compared with 1 of the 6 in the control group. The treatment as assessed by serial blood draws and clinical investigation, was safe and well tolerated. These data suggest that the intratumoral treatment with IL-18 and IL-12-encoding plasmid DNA has antitumor effects, which is well tolerated and thus holds promise for the treatment of patients with metastatic melanoma.
机译:黑色素瘤是灰马发病率很高的疾病,转移性疾病的治疗选择有限。基因治疗已在动物模型和人类患者中取得了一些成功。进行了一项随机双盲,安慰剂对照研究,以研究使用细胞因子编码质粒DNA在患有转移性黑素瘤的马匹中诱导免疫抗肿瘤作用的2种治疗方案。患有自发性转移性黑色素瘤(n = 26)的成年灰马被纳入研究。用转移性黑素瘤治疗26匹灰马,分别由瘤内注射编码白介素18的质粒DNA,编码白介素12的质粒DNA或空质粒DNA(对照组)组成。使用超声和卡尺测量以及肿瘤活检组织学评估来评估肿瘤反应。在接受IL-18和IL-12编码质粒DNA的治疗组中均可以显示出明显的肿瘤消退,而安慰剂治疗的对照组患者在治疗过程中显示出肿瘤的生长。另外,用IL-18或IL-12治疗的马中10个肿瘤中有7个在治疗后表现出肿瘤周围和/或肿瘤内炎性浸润,而对照组中的6个中只有1个。通过连续抽血和临床研究评估的治疗是安全且耐受性良好的。这些数据表明用IL-18和编码IL-12的质粒DNA进行的肿瘤内治疗具有抗肿瘤作用,其耐受性良好,因此有望用于治疗转移性黑色素瘤患者。

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