Thymosin Alpha-1
Thymalfasin · Tα1
Immunomodulatory peptide of thymic origin
About Thymosin Alpha-1
Thymosin alpha-1 is a 28-amino-acid peptide, acetylated at the N-terminus, originally isolated from the thymus.
It acts as a modulator of the immune response, mainly through Toll-like receptors (TLRs) on dendritic cells, favoring T-lymphocyte maturation and the Th1-type response. Synthetic thymalfasin is approved in more than 35 countries for hepatitis B and C and as an immune stimulant and adjuvant.
Quick guide · 5 key points
Thymosin Alpha-1 and the immune system
Thymosin alpha-1 is a thymus-derived peptide that modulates the immune response and is approved by regulators in a number of countries. Here are five things the research shows.
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1
It activates dendritic cells
Thymosin alpha-1 has been shown to drive dendritic cell maturation and IL-12 production through Toll-like receptor signaling (MyD88 pathway). In highly susceptible transplanted mice, it was associated with a Th1 response and protection against aspergillosis.1
TLRToll-like receptors: the pathway it uses to activate immunity -
2
Viral response in chronic hepatitis B
In a randomized trial in 98 patients with chronic hepatitis B, a 26-week course was associated with a complete virological response of 40.6% vs. 9.4% in the control group at 18 months. No significant side effects were observed.2
40.6%complete virological response vs. 9.4% untreated -
3
As an add-on for vaccines and cancer
In 90 men aged 65 to 99, it was associated with a stronger antibody response to the flu vaccine than placebo. In 488 patients with metastatic melanoma, adding it to dacarbazine (with or without interferon) was associated with more tumor responses (10 and 12 vs. 4 in the control arm), with no added toxicity.3,4
488patients with melanoma in the randomized trial -
4
Sepsis: the large trial was negative
In a trial of 361 patients with severe sepsis, 28-day mortality was 26.0% vs. 35.0%, a marginal result. But the double-blind phase 3 TESTS trial (1,106 adults) found no difference: 23.4% vs. 24.1%.5,6
23.4% vs 24.1%28-day mortality in phase 3 TESTS: no difference -
5
Approved in many countries and well tolerated
Synthetic thymosin alpha-1 is approved in more than 35 countries for hepatitis B and C and as an immune stimulant and adjuvant. The trials above reported no meaningful toxicity, and in phase 3 TESTS no safety outcome differed from placebo.7,2,3,4,6
35+countries with regulatory approval (2009 data)
References
- Romani L, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103(11):4232-9. PMID 14982877
- Chien RN, et al. Efficacy of thymosin alpha1 in patients with chronic hepatitis B: a randomized, controlled trial. Hepatology. 1998;27(5):1383-7. PMID 9581695
- Gravenstein S, et al. Augmentation of influenza antibody response in elderly men by thymosin alpha one. A double-blind placebo-controlled clinical study. J Am Geriatr Soc. 1989;37(1):1-8. PMID 2642497
- Maio M, et al. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J Clin Oncol. 2010;28(10):1780-7. PMID 20194853
- Wu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013;17(1):R8. PMID 23327199
- Wu J, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial. BMJ. 2025;388:e082583. PMID 39814420
- Goldstein AL, Goldstein AL. From lab to bedside: emerging clinical applications of thymosin alpha 1. Expert Opin Biol Ther. 2009;9(5):593-608. PMID 19392576
Structure and sequence
Sequence
Ac-SDAAVDTSSEITTKDLKEKKEVVEEAEN
Large molecule (3108.3 g/mol): the full structure is shown above; the sequence summarizes its amino-acid order. 3D model available on PubChem.
Five findings from studies
Summary of results reported in the scientific literature. Each finding describes what was observed in the cited study, in its specific population and conditions; it does not constitute a therapeutic indication.
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Clinical study
In a randomized trial in 98 patients with chronic hepatitis B, a 26-week course of thymosin alpha-1 has been associated with a complete virological response rate of 40.6% versus 9.4% in the control group at 18 months.
Chien RN et al. Hepatology. 1998;27:1383-1387 · PMID 9581695 -
Clinical study
In a double-blind trial in 90 men aged 65 to 99, thymosin alpha-1 has been associated with a better antibody response to the influenza vaccine versus placebo.
Gravenstein S et al. J Am Geriatr Soc. 1989;37:1-8 · PMID 2642497 -
Clinical study
In a randomized phase 2 trial in 488 patients with metastatic melanoma, the addition of thymosin alpha-1 to dacarbazine has been associated with higher tumor response rates, without additional toxicity.
Maio M et al. J Clin Oncol. 2010;28:1780-1787 · PMID 20194853 -
In vitro
In in vitro studies, thymosin alpha-1 has shown activation of dendritic cells through Toll-like receptors.
Romani L et al. Blood. 2004;103:4232-4239 · PMID 14982877 -
Regulatory
Thymalfasin has regulatory approval in more than 35 countries for indications that include chronic hepatitis B and C and use as an immunostimulant and adjuvant.
Goldstein AL, Goldstein AL. Expert Opin Biol Ther. 2009;9:593-608 · PMID 19392576
