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用于预防性和治疗性疫苗接种的细胞因子基因修饰肿瘤细胞:白细胞介素-2、γ干扰素或白细胞介素-2 + γ干扰素联合使用

Cytokine gene-modified tumor cells for prophylactic and therapeutic vaccination: IL-2, IFN-gamma, or combination IL-2 + IFN-gamma.

作者信息

Kircheis R, Küpcü Z, Wallner G, Wagner E

机构信息

Bender & Co GmbH, Vienna, Austria.

出版信息

Cytokines Cell Mol Ther. 1998 Jun;4(2):95-103.

PMID:9681248
Abstract

Murine melanoma cells were engineered to express interleukin-2 (IL-2), interferon-gamma (IFN-gamma) or both cytokines at various dose levels by means of the adenovirus-enhanced transferrinfection (AVET) method. The gene-modified cells were tested for their potency to induce an antitumor immune response in two experimental settings with different tumor load. In a prophylactic vaccination model, both IL-2 and IFN-gamma showed a dose-dependent protection against tumor cell challenge in two melanoma models. In the therapeutic vaccination model, where mice with measurable tumors were treated, immunization with IL-2 or IFN-gamma gene-modified cells led to complete tumor regression in 30% or 20% of the tumor-bearing animals respectively. The combination of IL-2 + IFN-gamma resulted in complete tumor regression in up to 50% of the tumor-bearing mice.

摘要

通过腺病毒增强转导感染(AVET)方法,对小鼠黑色素瘤细胞进行基因工程改造,使其在不同剂量水平下表达白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)或同时表达这两种细胞因子。在两种具有不同肿瘤负荷的实验环境中,对基因修饰细胞诱导抗肿瘤免疫反应的能力进行了测试。在预防性疫苗接种模型中,IL-2和IFN-γ在两种黑色素瘤模型中均显示出对肿瘤细胞攻击的剂量依赖性保护作用。在治疗性疫苗接种模型中,对患有可测量肿瘤的小鼠进行治疗,用IL-2或IFN-γ基因修饰细胞免疫分别导致30%或20%的荷瘤动物肿瘤完全消退。IL-2 + IFN-γ联合使用可使高达50%的荷瘤小鼠肿瘤完全消退。

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