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▎Thymosin Alpha-1 Overview
Thymosin Alpha-1 (Thymalfasin), a naturally occurring polypeptide in the thymus composed of 28 amino acids, possesses immunomodulatory functions. It regulates immune system function by enhancing the Th1 immune response and promoting the differentiation and maturation of T cells. Thymosin Alpha-1 has demonstrated therapeutic potential in various diseases, including chronic hepatitis B and C, AIDS, primary immunodeficiency diseases, and cancer. Additionally, it exhibits significant effects in enhancing vaccine responses and improving immunological dysfunction. Its advantages lie in high safety, good tolerability, and the ability to enhance the body's defense against infections and tumors through immune system regulation, particularly holding important clinical application value in immunocompromised or immunodysregulated conditions.
▎Thymosin Alpha-1 Structure
Source: PubChem | Sequence: SDAAVDTSSEITTKDLKEKKEVVEEAEN Molecular Formula: C129H215N33O55 Molecular Weight: 3108.3 g/mol CAS Number: 62304-98-7 PubChem CID: 16130571 Synonyms: Thymalfasin;Zadaxin |
▎Thymosin Alpha-1 Research
What is Thymosin Alpha-1?
Thymosin Alpha-1 is a polypeptide composed of 28 amino acids. It naturally exists in the thymus and plays a crucial role in the maturation and differentiation process of T cells.
What is the research background of Thymosin Alpha-1?
Thymosin Alpha-1 is a bioactive polypeptide isolated and purified from thymosin fraction 5, consisting of 28 amino acids. The thymus is an important organ of the immune system, which produces various substances that regulate immune function, and thymosin is one of them. With the in-depth study of the functions of the thymus, people have gradually realized that the active components in it may have potential value for the treatment of various diseases.
What is the mechanism of action of Thymosin Alpha-1?
Immunomodulation:
Thymosin Alpha-1 is a biological response modifier that can activate various cells in the immune system. It mainly regulates immune function by enhancing the differentiation and maturation of T cells (Sjogren M H, 2004; Mao L, 2023). Specifically, Thymosin Alpha-1 may affect thymocytes by stimulating their differentiation or transforming them into active T cells.
Anti-inflammatory mechanism:
In the treatment of COVID-19 pneumonia, Thymosin Alpha-1 accelerates the recovery from pneumonia through its anti-inflammatory mechanism. It can reduce the inflammatory response, promote the alleviation of COVID-19 pneumonia-related symptoms such as fever and fatigue, facilitate the absorption of exudate, and accelerate the recovery from COVID-19 pneumonia (Wang Z, 2023).
How does Thymalfasin induce the apoptosis of tumor cells in cancer treatment?
Enhancing the activity of immune cells:
Thymalfasin is a synthetic thymopeptide with high immune-enhancing activity. It can enhance the killing effect of immune cells on tumor cells, thereby indirectly inducing the apoptosis of tumor cells. For example, in the tumor microenvironment, Thymalfasin can promote the differentiation and maturation of T cells and enhance the activity of T cells. As an important part of the immune system, T cells can recognize and attack tumor cells, inducing the apoptosis of tumor cells by releasing cytotoxic substances and other means.
Regulating the immune response:
As an immunopotentiator, Thymalfasin can regulate the immune response and induce the apoptosis of tumor cells. It can enhance the Th1 immune response. Th1 cells mainly secrete cytokines such as IFN-γ, which can directly act on tumor cells and induce their apoptosis. In addition, Thymalfasin can also regulate the functions of other immune cells, such as enhancing the activity of NK cells. NK cells can directly kill tumor cells and also induce the apoptosis of tumor cells by secreting cytokines and other methods[1].
Improving the immunosuppression during anti-tumor treatment:
During the process of tumor treatment, patients often experience immunosuppression, which will affect the effectiveness of tumor treatment. Thymalfasin can improve the immunosuppression generated during anti-tumor treatment, enhance the ability of the immune system to attack tumor cells, and thus induce the apoptosis of tumor cells. For example, during chemotherapy or radiotherapy, the patient's immune system will be damaged to a certain extent. Thymalfasin can promote the recovery and proliferation of immune cells, improve the function of the immune system, and enhance the killing effect on tumor cells.
Thymosin alpha 1 has a wide range of biological activities.
Source:PubMed[6]
What are the applications of Thymalfasin?
Viral infections:
Due to its immunomodulatory effect, Thymosin Alpha-1 is often used to treat viral infections. For example, during the COVID-19 pandemic, it has shown good clinical efficacy in the treatment of COVID-19 pneumonia. Research shows that Thymosin Alpha-1 can prevent the progression of common COVID-19 infections to severe pneumonia through various immune-enhancing and anti-inflammatory protection mechanisms[2]. Specifically, for patients treated with Thymosin Alpha-1, the hospital stay was significantly shortened, the proportion of relief of pneumonia-related symptoms (such as fever and fatigue) was significantly higher than that of the control group, and the area of inflammatory exudation shown by CT was also significantly lower than that of the control group[2]. In addition, multivariate Cox model analysis showed that the patients who used Thymosin Alpha-1 and the younger patients had a significantly faster negative conversion rate of COVID-19 antigens[2]. Tα1 (the main component of Thymosin Alpha-1) increased the CD4+ T cell count in patients with low-flow oxygen inhalation support at baseline faster than standard treatment, and may play a role in the treatment of hospitalized patients with hypoxemia and lymphopenia caused by COVID-19[3].
Treatment of hepatitis:
Thymosin Alpha-1 also has a certain effect in the treatment of hepatitis. It can be used as a monotherapy for hepatitis B or in combination with interferon α-2b for the treatment of hepatitis C. Specifically, a study found that in the treatment of hepatitis B, the efficacy of Thymosin Alpha-1 was evaluated in four clinical trials involving 195 patients. In one of the studies, 9 out of 17 patients treated with Thymosin Alpha-1 had hepatitis B virus (HBV) DNA clearance at six months, compared with 10 out of 16 patients treated with interferon α-2b and 4 out of 15 patients in the historical control group.
Adjuvant treatment: Thymosin Alpha-1 is also widely used in cancer treatment. For patients with resectable non-small cell lung cancer (NSCLC) and liver cancer, in adjuvant treatment, Thymosin Alpha-1 can significantly improve the overall survival rate (OS) (Mao L, 2023). For patients with locally advanced unresectable NSCLC, Thymosin Alpha-1 can significantly reduce lymphopenia and pneumonia caused by radiotherapy and chemotherapy, and there is a trend of improving OS[4].
Enhancing anti-tumor immunity:
Preclinical evidence shows that Thymosin Alpha-1 may reverse the M2 polarization induced by the efferocytosis of macrophages by activating the TLR7/SHIP1 axis, enhance the efficacy of cancer chemotherapy, and enhance anti-tumor immunity by transforming "cold tumors" into "hot tumors" (Mao L, 2023). In addition, Thymosin Alpha-1 also has a protective effect in reducing colitis caused by immune checkpoint inhibitors (ICIs) and may enhance the clinical efficacy of ICIs[4]. Tα1 as adjuvant treatment after liver cancer resection may improve the prognosis of patients with small hepatocellular carcinoma. In a retrospective cohort study, patients with small hepatocellular carcinoma who underwent liver resection were divided into two groups, group A (resection + Tα1) and group B (resection only). After a median follow-up of 47.0 months, the 1-, 3-, and 5-year overall survival rates and recurrence-free survival rates of patients in group A were higher than those in group B. Multivariate analysis showed that Tα1 was an independent prognostic factor for overall survival rate and recurrence-free survival rate[5].
Restoring immune function and vaccine enhancement:
Thymosin Alpha-1 can be used to treat immunocompromised states and malignancies and as an enhancer of vaccine responses[4, 6]. It can regulate the immune system and enhance T cell function, and may have clinical benefits for diseases with impaired or ineffective immune function such as acute and chronic infections, cancer, and vaccine non-response[4]. Studies have proven that in severe sepsis, Thymosin Alpha-1 has been shown to restore immune function and help reduce the mortality rate of patients[4].
Preventing COVID-19 infections and complications in patients undergoing renal dialysis:
Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) are considered particularly vulnerable to SARS-CoV2 infection due to factors such as older age, comorbidity burden, drug use, and the need to visit dialysis clinics frequently. Early studies have shown that Thymosin Alpha-1, as an adjuvant to the influenza vaccine, can enhance the antibody response of the elderly population (including HD patients) to the influenza vaccine and reduce influenza infections. In the early days of the COVID-19 pandemic, researchers speculated that administering Thymosin Alpha-1 to HD patients could reduce the incidence and severity of COVID-19 infections. As of July 1, 2022, 254 ESRD/HD patients from five dialysis centers in Kansas City, Missouri were included in the study, of which 194 patients were randomly divided into group A (subcutaneous injection of 1.6mg Thymosin Alpha-1 twice a week for 8 weeks) and group B (control group, without receiving Thymosin Alpha-1)[7].
In conclusion, as a polypeptide with unique immunomodulatory functions, Thymosin Alpha-1 has shown potential applications in many aspects in the medical field. In the treatment of viral infections, it has a significant effect on diseases such as hepatitis B and COVID-19. It can not only accelerate the alleviation of symptoms and reduce inflammation but also prevent the progression of the disease and improve the recovery rate of patients. In terms of tumor treatment, it can induce the apoptosis of tumor cells through multiple pathways, enhance the killing effect of immune cells on tumor cells, and improve the immunosuppressive state, showing positive performance in the treatment of various cancers such as lung cancer and liver cancer.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Wang Z is a researcher with a diverse academic background and extensive collaborative experience across multiple institutions. Their research interests span interdisciplinary fields such as Engineering, Spectroscopy, Chemistry, Dentistry, Oral Surgery & Medicine, and Physics. Wang Z has been affiliated with prominent organizations and universities, including the University of Chinese Academy of Sciences (CAS), Yunnan University, Peking University, Hunan Agricultural University, Shanghai Jiao Tong University, and many others. Their work reflects a strong focus on innovation and collaboration, particularly in areas related to light industrial optoelectronic engineering, medical applications, and advanced materials science. Through partnerships with institutions like the Jiangsu Provincial Research Center for Light Industrial Optoelectronic Engineering & Technology and the Air Force Military Medical University, Wang Z has contributed to both theoretical advancements and practical applications in their fields of expertise. Wang Z is listed in the reference of citation [2].
▎Relevant Citations
[1] Sjogren M H. Thymalfasin: an immune system enhancer for the treatment of liver disease.[J]. Journal of Gastroenterology and Hepatology, 2004,19 Suppl 6:S69-S72. DOI:10.1111/j.1440-1746.2004.03635.x
[2] Wang Z, Wang C, Fei X, et al. Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms[J]. Pneumonia, 2023,15(1).DOI:10.1186/s41479-023-00116-6.
[3] Shehadeh F, Benitez G, Mylona E K, et al. A Pilot Trial of Thymalfasin (Thymosin-α-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection[J]. Journal of Infectious Diseases, 2023,227(2):226-235.DOI:10.1093/infdis/jiac362.
[4] Mao L. Thymosin alpha 1-Reimagine its broader applications in the immuno-oncology era[J]. International Immunopharmacology, 2023,117.DOI:10.1016/j.intimp.2023.109952.
[5] He C, Peng W, Li C, et al. Thymalfasin, a promising adjuvant therapy in small hepatocellular carcinoma after liver resection[J]. Medicine, 2017,96(16).DOI:10.1097/MD.0000000000006606.
[6] Dominari A, Hathaway Iii D, Pandav K, et al. Thymosin alpha 1: A comprehensive review of the literature.[J]. World Journal of Virology, 2020,9(5):67-78.DOI:10.5501/wjv.v9.i5.67.
[7] Tuthill C W, Awad A, Parrigon M, et al. A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report[J]. International Immunopharmacology, 2023,117.DOI:10.1016/j.intimp.2023.109950.
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