Thymosin alpha 1: A comprehensive review of the literature

Table 1 Summarizing pre-clinical and clinical studies

Pre-clinical studies
Ref.	Year	Application of thymosin alpha 1
Guo et al[36]	2015	The anti-tumor effect of thymosin alpha 1 was studied on human cancer cell lines. The study concluded that thymosin alpha 1 can decrease proliferation and induce apoptosis in human leukemia, non-small cell lung cancer, melanoma, and other cancers. The study concluded that thymosin alpha 1 could be an approach to breast cancer treatment
Clinical studies
Sherman et al[29]	2010	Thymosin alpha 1 was tested as monotherapy and in combination with interferon-alpha for the treatment of chronic hepatitis B. It was also shown to stimulate IL-2 receptor expression and IL-2 internalization and to enhance immune response in patients with immunodeficiency
Eckert et al[30]	1994	Combination therapy of thymosin alpha 1 and pegylated interferon alpha 2a preferred over interferon monotherapy for the treatment of chronic hepatitis C
Li et al[8]	2015	Significant decrease in mortality due to multiple organ failure in patients with sepsis
Li et al[6]	2010	Thymosin alpha 1 can be safely used as an adjuvant to antiretroviral therapy in HIV patients. It helps increase CD4+ count, stimulates the function of CD4+ cells, and helps decrease viral load. By amplifying the activity of catalase, superoxide dismutase, and glutathione peroxidase, it decreases oxidative damage to tissues. Thymosin alpha 1 reduces tumor cell proliferation in human malignancies by decreasing oxidative stress
Matteucci et al[2]	2017	Thymosin alpha 1 significantly increases levels of sjTREC in patients with advanced HIV disease
Camerini et al[1]	2015	Thymosin alpha 1 can be used in pseudomonas infections or infections following bone marrow transplant
Antachopoulos et al[7]	2012	Thymosin alpha 1 might be effective against mold toxicity
King et al[13]	2016	Thymosin alpha 1 increases cytokine production and is expected to be beneficial in immunocompromised patients
Pica et al[4]	2018	It has been postulated that thymosin alpha 1 can help regulate immunity and reduce inflammation in patients with psoriatic arthritis
Panatto et al[31]	2011	Thymosin alpha 1 has shown promising results as an adjuvant to the influenza vaccine
Carraro et al[3]	2012	Thymosin alpha 1 improves immunogenicity of the influenza vaccine
Qin et al[32]	2009	Thymosin alpha 1 can reduce oxidative damage to the pancreas and mitigate the risk of resulting diabetes
Costantini et al[33]	2019	Thymosin alpha 1 has shown promising results in patients with malignancies, such as metastatic melanoma, head and neck carcinoma, lung cancer, breast cancer, and hepatocellular carcinoma
Romani et al[21]	2007	A single-blind randomized control trial was conducted in six tertiary hospitals in China to study the beneficial effects of thymosin alpha 1 on patients with sepsis. The results showed 9% lower mortality in the treatment group compared to the control group
Sugahara et al[37]	2002	Patients with chronic hepatitis B who were treated with thymosin alpha 1 showed an overall improvement in serum ALT levels. ALT levels were reduced to normal in 42.9%. A total disappearance of serum HBV DNA was noted in 28.6% of patients

IL: Interleukin; sjTREC: Signal joint T cell receptor excision circles; HIV: Human immunodeficiency virus; ALT: Glutamic-pyruvic transaminase; HBV: Hepatitis B virus; DNA: Deoxyribonucleic acid.

Table 2 Summary of ongoing clinical trials of thymosin and coronavirus disease 2019

Clinical trial number	Location	Status	Condition	Intervention	Results
NCT04428008	United States	Not yet recruiting	COVID-19	Drug: Thymalfasin	Not yet available
NCT04487444	United States	Recruiting	COVID-19	Drug: Thymalfasin	Not yet available
NCT04268537	China	Not yet recruiting	COVID-19	Drug: PD-1 blocking antibody + standard treatment; Drug: Thymosin + Standard treatment; Other: Standard treatment	Not yet available
NCT04320238	China	Recruiting	COVID-19	Drug: Recombinant human interferon Alpha-1b; Drug: Thymosin alpha 1	Not yet available

Data retrieved from clinicaltrials.gov on October 5^th, 2020. COVID-19: Coronavirus disease 2019.