Immunomodulatory

Thymosin Alpha-1

Research Reagent · Laboratory Use Only

Quick Answer

What does research show about Thymosin Alpha-1 and immune system modulation?

Thymosin Alpha-1 (Tα1) is a 28-amino acid peptide derived from thymosin fraction 5, studied for its immunomodulatory properties. Research published in PubMed-indexed journals indicates it enhances T-cell maturation, dendritic cell function, and cytokine regulation. Preclinical and clinical studies have explored its role in infectious disease, cancer immunotherapy, and vaccine adjuvancy.

PMID41887933↗DOI10.2147/IDR.S34301↗⟳ Reconstitution Calculator
Scientific AbstractPMID 41887933 · 2026

Background

Thymosin α1 (Tα1) has been shown to improve survival in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), but its immunomodulatory mechanisms remain unclear. This study investigated how Tα1 restores immune homeostasis to confer a survival benefit in these patients.

Methods

In this open-label, randomized controlled trial (NCT03082885), 73 patients with HBV-ACLF received either standard medical therapy (SMT, n = 38) or SMT plus Tα1 (n = 35). Peripheral blood immune cell subsets were analyzed by flow cytometry and serum cytokine levels were measured by ELISA. Patients were stratified by 90-day transplant-free survival.

Results

Patients who survived at 90 days exhibited a higher proportion of effector T (TE) cells and lower levels of regulatory T cells (Tregs) at baseline compared to non-survivors. Survivors also had significantly higher initial levels of pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) and lower levels of TGF-β. Over time, survivors showed a gradual decline in inflammatory markers, whereas non-survivors developed a progressive inflammatory storm. Tα1 treatment significantly increased 90-day transplant-free survival and was associated with reduced frequencies of Tregs and CD226low/- Treg subsets at weeks 4-8. Tα1 also moderated the late-stage hyperinflammatory response without compromising early immune activation.

Conclusions

Tα1 improves clinical outcomes in HBV-ACLF by rebalancing the immune response-mitigating excessive inflammation and preventing immune paralysis by modulating T-cell differentiation and cytokine production, thereby breaking the cycle of hyperinflammation and immunosuppression that characterizes ACLF progression.

Source:10.2147/IDR.S34301
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Thymosin Alpha-1?

Thymosin α1 (Tα1) is an immunomodulatory peptide that restores immune homeostasis in hepatitis B virus-related acute-on-chronic liver failure by rebalancing T-cell differentiation and cytokine production. In clinical trials, Tα1 administration significantly improved 90-day transplant-free survival rates in ACLF patients receiving standard medical therapy.

Mechanism of Action

Thymosin α1 exerts its therapeutic effect through dual immunoregulatory pathways. The peptide suppresses excessive regulatory T cell (Treg) expansion while preserving early-stage effector T cell (TE) activation, thereby preventing both immune paralysis and hyperinflammatory cascade collapse. Mechanistically, Tα1 modulates CD226low/- Treg subset frequencies and dampens late-stage pro-inflammatory cytokine production (IL-6, TNF-α, IFN-γ, TGF-β) without compromising critical early immune activation necessary for viral control and tissue repair.

Observed Laboratory Results

  • Treg suppression: Tα1 treatment significantly reduced regulatory T cell frequencies and CD226low/- Treg subset proportions at weeks 4-8, restoring the TE:Treg balance disrupted in non-survivors
  • Cytokine moderation: Tα1-treated survivors exhibited gradual decline in pro-inflammatory markers (IL-6, TNF-α, IFN-γ) while maintaining early immune activation, preventing both hyperinflammatory storm and immunosuppressive collapse
  • Clinical outcome: Tα1 co-administration with standard medical therapy increased 90-day transplant-free survival rates in the randomized controlled trial (NCT03082885) versus SMT monotherapy
Clinical Research Parameters
10 trials4 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT02366247 ↗
UNKNOWNPhase IIIn=463

Phase Ⅲ Trial for Combination Treatment of PEG-Tα1 and Adefovir for HBeAg-positive Chronic Hepatitis B

This trial is to assess the efficacy and safety of Polyethylene Glycol thymosin alpha1 (PEG-Tα1), a new long immunomodulator (Category 1.1 of Chemical Drugs) being developed from Hansoh Pharmaceutical of China, in combination with adefovir in HBeAg-positive patients with chronic hepatitis B.

Study Interventions
PEG-Tα1, Placebo to match PEG-Tα1, Adefovir
Primary Endpoints
Loss of HBeAg
Study Period
2013-08 → 2016-02
NCT03082885 ↗
COMPLETEDN/An=120

The Efficacy and Safety of Thymosin-α1 in Patients With HBV-related ACLF

A randomized controlled trial to evaluate efficacy and safety of Thymosin-α1 administration in patients with HBV-related Acute-on-chronic liver failure.

Study Interventions
Thymosin-α1
Primary Endpoints
The liver transplantation-free survival rate of 90 days
Study Period
2017-04-10 → 2019-07-30
NCT00291616 ↗
COMPLETEDPhase IVn=52

Efficacy Study of Thymosin alpha1 & Pegylated Interferon-alpha2a to Treat Chronic Hepatitis B

The purpose of this study is to determine the optimal treatment duration of antiviral therapy for chronic hepatitis B.

Study Interventions
Pegylated Interferon-alpha2a, Thymosin alpha1 & Pegylated Interferon-alpha2a
Primary Endpoints
HBeAg seroconversion, HBV DNA titer<20,000 IU/mL
Study Period
2005-12 → 2008-08
NCT02787447 ↗
UNKNOWNPhase IIn=46

Radiotherapy Combined With Thymosin for Metastatic NSCLC Patients Who Showed Stable Disease After First Line TKI Therapy

The investigators postulated that the exploitation of the pro-immunogenic effects of radiotherapy with thymosin might result in abscopal responses among patients with metastatic cancer. The research is designed to evaluate the efficacy and toxicity of patients treated with hypofractionated radiotherapy combined with thymosin alpha 1. An exploratory biomarker analysis in blood and tumor samples is

Study Interventions
TKI, Thoracic Hypofractionated Radiotherapy, Thymosin Alpha 1
Primary Endpoints
The proportion of patients with an abscopal response assessed at 1-6 months after the radiation therapy
Study Period
2016-05 → 2020-05
NCT02535988 ↗
WITHDRAWNPhase II0

Abscopal Effect for Metastatic Colorectal Cancer

Patients with colorectal cancer that had metastatic lesions after been treated with definitive surgery or chemoradiotherapy are being asked to participate in this study. 1. To observe immunity-mediated tumor response outside the radiation field (abscopal effect) after chemoradiotherapy of a metastatic site in metastatic colorectal cancer patients. 2. To induce the efficacy (effectiveness) of a ne

Study Interventions
Radiation therapy, Thymalfasin
Primary Endpoints
The proportion of patients with an abscopal response assessed at 7-8 weeks after the initiation of treatment.
Study Period
2015-09 → 2017-12
NCT07103408 ↗
NOT YET RECRUITINGPhase IIn=56

A Study Evaluating Concurrent Chemoradiotherapy Combined With Dual Immune Checkpoint Blockade for Limited-stage Small Cell Lung Cancer

This study will enroll patients with limited-stage small cell lung cancer (SCLC). Patients will receive chemotherapy (etoposide and platinum-based drugs) combined with dual immune checkpoint blockade (PD-1/CTLA-4) and thymosin alpha 1, with a total cycles of 4. Thoracic radiotherapy was performed no later than the three cycle of chemotherapy. Prophylactic cranial irradiation was recommended for pa

Study Interventions
Immuno-chemotherapy, Radiotherapy, Consolidative therapy
Primary Endpoints
Progression-free survival
Study Period
2025-10-01 → 2029-09-30
NCT04963712 ↗
COMPLETEDEarly Phase In=20

Zadaxin and HIV-positive Patients With Immune Reconstitution Disorder

The purpose of this study is to evaluate the safety and efficacy of Zadaxin® in the treatment of HIV-positive patients with immune reconstitution disorders. Researchers previously used Zadaxin® (Thymosin α-1, Tα1) as an immune adjuvant for people infected with HIV-1 and found that Tα1 and Interferon-α (IFN-α) have a synergistic effect in immune enhancement. In addition, studies have found that the

Study Interventions
Zadaxin
Primary Endpoints
Change in CD4+T cell counts; Change in CD4/CD8 ratio
Study Period
2021-09-01 → 2022-08-11
NCT04524169 ↗
UNKNOWNPhase IVn=100

Immunotherapy for Elderly Patients With Chronic Osteoporotic Pain

Osteoporotic pain is the most common clinical symptom in elderly patients. The course of pain is prolonged and the effect of clinical treatment is limited. This study will observe the therapeutic effect of thymosin alpha 1 on elderly patient with osteoporotic pain and explore its immunotherapy mechanism.

Study Interventions
Thymosin Alpha1
Primary Endpoints
Change of VAS scores
Study Period
2020-11-01 → 2021-12-31
NCT02906150 ↗
UNKNOWNPhase IIn=140

Thymosin Alpha 1 Plus Maintenance Therapy With the Standard of Care (SoC) in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC), EGFR Wild Type

Thymosin alpha 1 plus maintenance therapy with the Standard of Care (SoC) chemotherapy plus cisplatin (or carboplatin) in patients with metastatic Non-Small Cell Lung Cancer (NSCLC), EGFR wild type

Study Interventions
Thymalfasin (Thymosin alpha 1, Ta1), SoC (chemotherapy and platinum agent)
Primary Endpoints
Time to progression free survival (PFS)
Study Period
2016-09 → 2019-07
NCT01943617 ↗
COMPLETEDPhase IVn=606

Optimized Treatment and Regression of HBV-induced Compensated Liver Cirrhosis

Six hundreds patients with chronic hepatitis B clinically diagnosed as compensated liver cirrhosis are randomly assigned in a 1:1 ratio. One arm is entecavir alone for 2 years; the other is entecavir alone for the first 0.5 year, entecavir plus thymosin-α for 1 year, entecavir for another additional 0.5 year.Patients will be assessed at baseline, at every six months for blood cell count, liver fun

Study Interventions
Entecavir, Thymosin-α
Primary Endpoints
Decompensated rate of Liver Cirrhosis after 2 years treatment
Study Period
2013-06 → 2016-12
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Thymosin Alpha-1 is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 41887933) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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