title: Prothymosin Alpha and Immune Responses: Are We Close to Potential Clinical Applications?
abstract: The thymus gland produces soluble molecules, which mediate significant immune functions. The first biologically active thymic extract was thymosin fraction V, the fractionation of which led to the isolation of a series of immunoactive polypeptides, including prothymosin alpha (proTα). ProTα displays a dual role, intracellularly as a survival and proliferation mediator and extracellularly as a biological response modifier. Accordingly, inside the cell, proTα is implicated in crucial intracellular circuits and may serve as a surrogate tumor biomarker, but when found outside the cell, it could be used as a therapeutic agent for treating immune system deficiencies. In fact, proTα possesses pleiotropic adjuvant activity and a series of immunomodulatory effects (eg, anticancer, antiviral, neuroprotective, cardioprotective). Moreover, several reports suggest that the variable activity of proTα might be exerted through different parts of the molecule. We first reported that the main immunoactive region of proTα is the carboxy-terminal decapeptide proTα(100-109). In conjunction with data from others, we also revealed that proTα and proTα(100-109) signal through Toll-like receptor 4. Although their precise molecular mechanism of action is yet not fully elucidated, proTα and proTα(100-109) are viewed as candidate adjuvants for cancer immunotherapy. Here, we present a historical overview on the discovery and isolation of thymosins with emphasis on proTα and data on some immune-related new activities of the polypeptide and smaller immunostimulatory peptides thereof. Finally, we propose a compiled scenario on proTα's mode of action, which could eventually contribute to its clinical application.
authors.affiliation: Faculty of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Samara
authors.affiliation: Faculty of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, Greece; King's College London, Rayne Institute, London, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Ioannou
authors.affiliation: Faculty of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, Greece. Electronic address: rtsitsil@biol.uoa.gr.
authors.forename: O E
authors.initials: OE
authors.lastname: Tsitsilonis
mesh_terms: D000276:Adjuvants, Immunologic; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D018696:Neuroprotective Agents; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014777:Virus Diseases / Q000188:drug therapy / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin
keywords: Adjuvant; Alarmin; Cancer; DAMP; Immune response; Immunoenhancing peptide; ProTα(100–109); Prothymosin α; Thymic peptides