The present invention relates to the field of Biotechnology and more particularly to the mutated polypeptides of TGF² molecule whose primary sequence has a high homology with the sequence of human TGF². These muteins lose their ability to interact with ALK5 but maintain their ability to interact with other receptors that are part of the receptor complex (T²RII and T²RIII). They have the property of antagonizing the signaling of all natural variants of TGF² ligands, dependent of ALK5 recruitment in the receptor complex, and have significant immunomodulatory effects. The present invention relates to pharmaceutical compositions comprising as active principle the polypeptides or fusion proteins disclosed and their use thereof given their modulating effect on the immune system in diseases such as cancer, diseases accompanied by fibrosis and chronic infectious diseases.
