Garaci Enrico, Pica Francesca, Sinibaldi-Vallebona Paola, Pierimarchi Pasquale, Mastino Antonio, Matteucci Claudia, Rasi Guido
Dipartimento Medicina Sperimentale e Scienze Biochimiche, Università di Tor Vergata, Via Montpellier, 1-00133 Rome, Italy.
Int Immunopharmacol. 2003 Aug;3(8):1145-50. doi: 10.1016/S1567-5769(03)00053-5.
Multiple therapeutic approaches have been tested in different experimental tumour models and in human cancers. Most part of them are based on the hypothesis that the inhibition of tumour growth requires a strong immune response in which a main role is played by CTLs. It is known, however, that an efficient CTL response requires expression of tumour antigens, MHC class I surface molecules presentation, expression of different co-stimulatory molecules and a sustained generation and proliferation of specific cytotoxic CD8+ cells with an efficient CD4+ cooperation. In this context, our group has extensively explored a protocol of combined therapy consisting of the use of chemotherapeutic agents associated with thymosin alpha 1 (Talpha 1) and different cytokines, whose efficacy has been demonstrated in experimental models as well as in human cancers. In this manuscript, the main data supporting a pivotal role of Talpha 1 in such combination protocols are reviewed. In particular, a special mention of the molecular mechanisms underlying the effects of Talpha 1 on immune effector cells as well as on target tumour cells is provided. These data contribute to explain the mechanism of action of Talpha 1, when used in combination therapy, for the treatment of cancer and provide new insights in predicting further possible applications of this peptide in other pathological conditions.
多种治疗方法已在不同的实验性肿瘤模型和人类癌症中进行了测试。其中大部分基于这样的假设，即抑制肿瘤生长需要强大的免疫反应，而细胞毒性T淋巴细胞（CTL）在其中发挥主要作用。然而，众所周知，有效的CTL反应需要肿瘤抗原的表达、MHC I类表面分子的呈递、不同共刺激分子的表达以及具有高效CD4 + 细胞协作的特异性细胞毒性CD8 + 细胞的持续产生和增殖。在此背景下，我们团队广泛探索了一种联合治疗方案，该方案包括使用与胸腺肽α1（Tα1）和不同细胞因子相关的化疗药物，其疗效已在实验模型以及人类癌症中得到证实。在本手稿中，回顾了支持Tα1在这种联合方案中起关键作用的主要数据。特别提到了Tα1对免疫效应细胞以及靶肿瘤细胞作用的分子机制。这些数据有助于解释Tα1在联合治疗中用于治疗癌症的作用机制，并为预测该肽在其他病理状况下的进一步可能应用提供新的见解。
