What is Thymosin Alpha 1 (Tα1)?

Thymosin Alpha 1 (Tα1) is a peptide naturally produced by the thymus gland. A pleiotropic peptide stimulates or downregulates inflammation and immune function depending on the host’s state.

What is the Structure of Thymosin Alpha 1 (Tα1)?

Tα1 contains 28 amino acids with a molecular weight of 3KDa and is stable at 80–90 °C. The amino acid residues are N-terminally acetylated and proteolytically processed from prothymosin alpha. It was first isolated by Goldstein and coworkers from thymosin fraction 5 derived from calf thymus tissues. The amino acid sequence is as follows:
Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH

What are the Biological Activities of Thymosin Alpha 1 (Tα1)?

Immunoregulation
Several in vivo and in vitro studies have demonstrated the immune regulating potential of Thymosin Alpha 1 peptide. Tα1 assists in:

● Maturation of T-cells and converts precursor cells into differentiated and mature CD4+ and CD8+ T cells.
● Balancing the levels of CD3/CD4+/CD8+ T cells in the peripheral blood.
● Stimulating the action of Natural Killer (NK) cells and cytotoxic lymphocytes leads to the death of virally infected cells.
● Activating dendritic cells has been proven to reduce mortality in mice infected with aspergillosis.
● Regulating the levels of immune cytokines, such as increasing the levels of IL-2 and decreasing the levels of IL-4, IL-10, and IL-1B.

Antitumor Effects
Tα1 has been shown to reduce tumor cell proliferation in various in vivo and in vitro studies. The tumor models shown to be effective include primary hepatocarcinoma, primary lung adenocarcinoma, breast adenomas, glioblastoma, colorectal cancer, and metastatic spread to the liver and lungs. The antitumor effects of Tα1 are due to its ability to include apoptosis and its impact on a variety of inflammation, immune, and oxidative responses.

Antioxidant Effects
Tα1 reduces oxidative stress by increasing the activity of antioxidants such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). It also reduces molecules responsible for producing free radicals such as malondialdehyde (MDA).

Other Effects
Other biological effects of Tα1 include:
● It has neuro-excitatory effects, and its effect on excitatory transmission in hippocampal neurons has been demonstrated.
● When combined with chemotherapy, it can prevent chemotherapy-included neurotoxicosis.
● It can stimulate endothelial cell migration and angiogenesis. These effects might have some implications for promoting wound healing.
● Due to its immune regulating, anti-inflammatory, and antioxidant effects, Tα1 might be useful in various autoimmune and inflammatory conditions. Such conditions include cystic fibrosis, Lyme disease, and even COVID.

Clinical Applications of Thymosin Alpha 1 (Tα1)?

Tα1 has clinical applications in the following areas:

Cancer Therapy
In a phase II multi-center, randomized open-label study, a combination of Dacarbazine (DTIC) and different doses of Tα1 was given to patients with stage IV melanoma. Results showed that the therapy tripled the response rate and improved the overall survival by three months. Similarly, when combined with transarterial chemoembolization (TACE), the use of Tα1 significantly improved the treatment response and survival rates in patients with unresectable hepatocellular carcinoma.

Hepatitis B Treatment
Tα1 has been approved as a monotherapy for the treatment of hepatitis B in many countries. In Japanese research, giving Tα1 to hepatitis B-positive patients lead to seroconversion in up to 21.5% of patients with 48 weeks of therapy. Similarly, in a Chinese patient, Tα1 treatment led to complete remission, defined by normalization of alanine transaminase (ALT) and undetectable HBV DNA, in up to 42.3% of patients.

Hepatitis C Treatment
Tα1 is not effective as a monotherapy for hepatitis C treatment. However, the response rate can increase significantly when used in combination with peg-IFN and ribavirin therapy. HCV is a resistant infection, and even with dual peg-IFN and ribavirin therapy, the response rate can be as low as 50%. Therefore, T might be an effective adjuvant for hepatitis C management.

HIV/AIDS Treatment
The human immunodeficiency virus (HIV) targets body cells that express CD4, such as CD4+ lymphocytes and macrophages. Once the virus develops an affinity for lymphocytes (lymphotropic), it becomes highly efficient in targeting new CD4+ cells and becomes highly virulent. A solid immune response might be one way to prevent the infection and onset of HIV infection. In one study, triple therapy with IFN-α, zidovudine, and T significantly improved CD4+ function and low levels of HIV viral infections.

Summary

Thymosin Alpha 1 (Tα1) is a pleiotropic peptide with various immune-modulating, anti-inflammatory, anti-viral, antioxidant, and antitumor effects. Its potential use in health and disease warrants rigorous clinical research.

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