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IL2 treatment for cancer: from biology to gene therapy.

机译:IL2的癌症治疗:从生物学到基因治疗。

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摘要

In this review we shall discuss the biological rationale and the clinical findings obtained using Interleukin 2 (IL2)-based immunotherapy in the management of cancer patients. Objective and long-lived clinical responses have been documented in a proportion of cases, particularly renal cell carcinoma, melanoma and acute myeloid leukaemia. Though encouraging, the clinical use of IL2 has so far been limited by toxicity, as well as by the heterogeneous and unpredictable responses and by the lack of specific anti-tumour effect. These considerations have led to the belief that more sophisticated technologies aimed at introducing the IL2 gene into the neoplastic cells may potentially overcome some of the limitations coupled to the in vivo infusion of high doses of IL2. The data accumulated in animal models and, more recently, also with human tumour cells indicate that the IL2 gene may be successfully inserted into neoplastic cells. The constitutive secretion of IL2 by the tumour cells leads to a reduced or abrogated tumorigenicity in several different tumour models. The evidence that in some experimental tumours the transduction of the IL2 gene into the neoplastic cells may elicit a specific cytotoxic response and confer anti-tumour memory, suggests that vaccination protocols based on this innovative strategy may represent a potential new tool in the management of cancer patients.
机译:在这篇综述中,我们将讨论在癌症患者管理中使用基于白介素2(IL2)的免疫疗法获得的生物学原理和临床发现。在一些病例中,尤其是肾细胞癌,黑色素瘤和急性髓细胞性白血病,已记录了客观和长期的临床反应。尽管令人鼓舞,但迄今为止,IL2的临床使用受到毒性,异质性和不可预测的反应以及缺乏特异性抗肿瘤作用的限制。这些考虑导致人们相信,旨在将IL2基因引入赘生性细胞的更复杂的技术可能会克服一些与体内大剂量IL2输注相关的局限性。在动物模型中以及最近在人类肿瘤细胞中积累的数据表明,IL2基因可能已成功插入肿瘤细胞中。在几种不同的肿瘤模型中,肿瘤细胞组成性分泌IL2导致致瘤性降低或消失。在某些实验性肿瘤中,IL2基因转导进入赘生性细胞可能引发特定的细胞毒性反应并赋予抗肿瘤记忆的证据表明,基于这种创新策略的疫苗接种方案可能代表了癌症治疗中的一种潜在新工具耐心。

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