Thymosin alpha 1 in combination with cytokines and chemotherapy for the treatment of cancer

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 α 1 (Tα1) 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 Tα 1 in such combination protocols are reviewed. In particular, a special mention of the molecular mechanisms underlying the effects of Tα 1 on immune effector cells as well as on target tumour cells is provided. These data contribute to explain the mechanism of action of Tα1, 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. © 2003 Published by Elsevier Science B.V.