Immunopharmacology of Thymosin alpha 1 and Cytokine Synergy

• Published in: Annals of the New York Academy of Sciences Vol. 1112; no. 1; pp. 235 - 244
• Main Authors: Naylor, Paul H, Quadrini, Karen, GARACI, ENRICO, Rasi, Guido, Hadden, John W
• Format: Journal Article
• Language: English
• Published: 01.09.2007
• ISSN: 0077-8923; 1930-6547
• DOI: 10.1196/annals.1415.036

AbstractThymosin alpha 1 (T alpha 1) is a 28 amino acid biologically active protein cleaved from positions 2-29 of a precursor protein, prothymosin alpha . Since its discovery, T alpha 1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. T alpha 1 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 T alpha 1 may act via pathways commonly used by various cytokines. This raises the possibility that T alpha 1 and cytokines may have synergistic activity through potentiation of cytokine activity by T alpha 1. Improved control of tumor growth when tumor-bearing mice were treated with T alpha 1 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 T alpha 1 (IRX-3). Although IRX-2 was effective alone (using doses that contain significantly less IL-2 than in most typical studies), adding T alpha 1 led to significant improvement in survival of the tumor-bearing mice. Based on these observations, the immunopharmacology of T alpha 1 predicts an important clinical role for T alpha 1 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.