title: Immunopharmacology of thymosin alpha1 and cytokine synergy.
abstract: Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein cleaved from positions 2-29 of a precursor protein, prothymosin alpha. Since its discovery, Talpha1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. Talpha1 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 Talpha1 may act via pathways commonly used by various cytokines. This raises the possibility that Talpha1 and cytokines may have synergistic activity through potentiation of cytokine activity by Talpha1. Improved control of tumor growth when tumor-bearing mice were treated with Talpha1 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 Talpha1 (IRX-3). Although IRX-2 was effective alone (using doses that contain significantly less IL-2 than in most typical studies), adding Talpha1 led to significant improvement in survival of the tumor-bearing mice. Based on these observations, the immunopharmacology of Talpha1 predicts an important clinical role for Talpha1 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.
authors.affiliation: IRX Therapeutics Inc., 1 BioScience Park Drive, Farmingdale, NY 11735, USA. pnaylor@irxtherapeutics.com
authors.forename: Paul H
authors.initials: PH
authors.lastname: Naylor
authors.forename: Karen
authors.initials: K
authors.lastname: Quadrini
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Guido
authors.initials: G
authors.lastname: Rasi
authors.forename: John W
authors.initials: JW
authors.lastname: Hadden
mesh_terms: D000818:Animals; D016207:Cytokines / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D013947:Thymosin; D011493:Protein Kinase C; D000077596:Thymalfasin