Immunopharmacology of thymosin α1 and cytokine synergy

Thymosin α1 (Tα1) is a 28 amino acid biologically active protein cleaved from positions 2-29 of a precursor protein, prothymosin α. Since its discovery, Tα1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. Tα1 administration is highly effective in settings where irradiation, chemotherapy, tumor burden, or immune senescence have caused a reduction of T cell number and/or function. Recent in vitro studies, including the one reported here, suggest that Tα1 may act via pathways commonly used by various cytokines. This raises the possibility that Tα1 and cytokines may have synergistic activity through potentiation of cytokine activity by Tα1. Improved control of tumor growth when tumor-bearing mice were treated with Tα1 and high doses of IL-2 has been previously reported. We extended those studies with the Lewis lung carcinoma mouse model using IRX-2, a natural well-defined biologic containing multiple cytokines, in combination with Tα1 (IRX-3). Although IRX-2 was effective alone (using doses that contain significantly less IL-2 than in most typical studies), adding Tα1 led to significant improvement in survival of the tumor-bearing mice. Based on these observations, the immunopharmacology of Tα1 predicts an important clinical role for Tα1 in the restoration of cellular immune activity when used in combination with cytokines. Patients who experience immune suppression due to the presence of tumor, irradiation, and/or chemotherapy or aging of the host would most benefit from this treatment combination.