Foa R, Guarini A, Gansbacher B
Dipartimento di Scienze Biomediche e Oncologia Umana, Torino, Italy.
Br J Cancer. 1992 Dec;66(6):992-8. doi: 10.1038/bjc.1992.400.
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.
在本综述中，我们将讨论在癌症患者管理中使用基于白细胞介素2（IL2）的免疫疗法所获得的生物学原理和临床发现。在一部分病例中，尤其是肾细胞癌、黑色素瘤和急性髓系白血病，已经记录到了客观且持久的临床反应。尽管令人鼓舞，但迄今为止，IL2的临床应用受到毒性、反应的异质性和不可预测性以及缺乏特异性抗肿瘤作用的限制。这些考虑因素促使人们相信，旨在将IL2基因导入肿瘤细胞的更先进技术可能会克服与体内输注高剂量IL2相关的一些局限性。在动物模型以及最近在人类肿瘤细胞中积累的数据表明，IL2基因可以成功插入肿瘤细胞。肿瘤细胞组成性分泌IL2会导致几种不同肿瘤模型中的肿瘤发生能力降低或消除。有证据表明，在一些实验性肿瘤中，将IL2基因转导到肿瘤细胞中可能引发特异性细胞毒性反应并赋予抗肿瘤记忆，这表明基于这种创新策略的疫苗接种方案可能成为癌症患者管理中的一种潜在新工具。
