Thymosin alpha 1: past clinical experience and future promise (original) (raw)
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From lab to bedside: emerging clinical applications of thymosin α1
Expert Opinion on Biological Therapy, 2009
Background: Thymosin α 1 (Tα 1), a synthetic version of a thymic-derived biological response modifier was the first of the thymosins in clinical use. Tα 1 is approved in over 35 countries for the treatment of hepatitis B and C, and as an immune stimulant and adjuvant. Tα 1 is also in late-stage clinical testing in the United States and Europe for hepatitis C and stage IV melanoma. Objective/methods: Novel applications and other recently completed trials point to much broader clinical applications of Tα 1 in the treatment of life-threatening and chronic diseases, and are the subject of this review. Result/conclusions: The most recent reports of clinical trials with Tα 1 are pointing to important, hitherto unrecognized, applications in a number of diseases and disorders, including septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients. It is also emerging as a promising chemoprotection agent in patients undergoing chemotherapy.
Jack of all trades: thymosin α1 and its pleiotropy
Annals of the New York Academy of Sciences, 2012
Thymosin ␣1 (T␣1), a thymosin-related 28-mer synthetic amino-terminal acetylated peptide, has gained increasing interest in recent years, due to its pleiotropy. The peptide has been used worldwide as an adjuvant or immunotherapeutic agent to treat disparate human diseases, including viral infections, immunodeficiencies, and malignancies. The peptide can enhance T cell, dendritic cell (DC), and antibody responses, modulate cytokine and chemokine production, and block steroid-induced apoptosis of thymocytes. Its central role in modulating DC function and activating multiple signaling pathways that contribute to different functions may offer a plausible explanation for its pleiotropic action. Additionally, the ability of T␣1 to activate the indoleamine 2,3-dioxygenase enzyme-which confers immune tolerance during transplantation and restrains the vicious circle of chronic inflammation-has been a turning point, suggesting a potential, specific function in immunity. Accordingly, T␣1 has recently been shown to promote immune reconstitution and improve survival of recipients of HLA-matched sibling T cell-depleted stem cell transplants in a phase I/II clinical trial. Thus, T␣1 continues to live up to its promises.
Thymosin Alpha 1: From Bench to Bedside
Annals of the New York Academy of Sciences, 2007
After the initial dramatic effects, observed in a Lewis lung carcinoma animal model, using a combination of thymosin alpha 1 (T␣1) and interferon (IFN) after cyclophosphamide, a number of other preclinical models in mice (Friend erythroleukemia and B16 melanoma) and in rats (DHD/K12 colorectal cancer liver metastasis) have confirmed the efficacy of the combination therapy with T␣1 and either IFN or IL-2 plus chemotherapy. These results provided the scientific foundation for the first clinical trials using T␣1 in combination with BRMs and/or chemotherapy. Pivotal trials in advanced non-small cell lung cancer (NSCLC) and melanoma with T␣1 and IFN-␣ low doses after cis-platinum or dacarbazine produced the first evidence of the high potentiality of this approach in the treatment of human cancer. The combination of T␣1 and IFN-␣ was also used in patients affected by chronic B and C hepatitis including IFN-nonresponders and infected by precore mutants or genotype 1b. Further studies demonstrated additional biological activities clarifying the mechanism of action of T␣1, partially explaining the synergism with IFN. It has been shown the capacity of activating infected dendritic cells through Toll-like receptor signaling, thus influencing the inflammation balance, and of increasing the expression of tumor, viral, and major histocompatibility complex (MHC) I antigens. Dose-response studies suggested the possibility of improving the efficacy of this molecule reducing the overall toxic. Based on these information
Annals of The New York Academy of Sciences, 2010
Published studies have described a number of physiological properties and cellular functions of thymosin β4 (Tβ4), the major G-actin-sequestering molecule in mammalian cells. Those activities include the promotion of cell migration, blood vessel formation, cell survival, stem cell differentiation, the modulation of cytokines, chemokines, and specific proteases, the upregulation of matrix molecules and gene expression, and the downregulation of a major nuclear transcription factor. Such properties have provided the scientific rationale for a number of ongoing and planned dermal, corneal, cardiac clinical trials evaluating the tissue protective, regenerative and repair potential of Tβ4, and direction for future clinical applications in the treatment of diseases of the central nervous system, lung inflammatory disease, and sepsis. A special emphasis is placed on the development of Tβ4 in the treatment of patients with ST elevation myocardial infarction in combination with percutaneous coronary intervention.
Annals of The New York Academy of Sciences, 2010
Published studies have described a number of physiological properties and cellular functions of thymosin β4 (Tβ4), the major G-actin-sequestering molecule in mammalian cells. Those activities include the promotion of cell migration, blood vessel formation, cell survival, stem cell differentiation, the modulation of cytokines, chemokines, and specific proteases, the upregulation of matrix molecules and gene expression, and the downregulation of a major nuclear transcription factor. Such properties have provided the scientific rationale for a number of ongoing and planned dermal, corneal, cardiac clinical trials evaluating the tissue protective, regenerative and repair potential of Tβ4, and direction for future clinical applications in the treatment of diseases of the central nervous system, lung inflammatory disease, and sepsis. A special emphasis is placed on the development of Tβ4 in the treatment of patients with ST elevation myocardial infarction in combination with percutaneous coronary intervention.
Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application
International Journal of Immunopharmacology, 2000
Many studies have explored the effects of immunotherapy, alone or in combination with conventional therapies, on both experimental and human cancers. Evidence has been provided that combined treatments with thymosin alpha 1 (T a 1) and low doses of interferon (IFN) or interleukin (IL)-2 are highly effective in restoring several immune responses depressed by tumor growth and/or cytostatic drugs. In addition, when combined with specific chemotherapy, they are able to increase the anti-tumor effect of chemotherapy while markedly reducing the general toxicity of the treatment. The advantages of using this combined chemo-immunotherapeutic approach in experimental and human cancers are reviewed in this issue. : S 0 1 9 2 -0 5 6 1 ( 0 0 ) 0 0 0 7 5 -8 E. Garaci et al.