Thymosin Alpha-1 Research & Studies

Immune and inflammatory disorders are part of the complex pathophysiological processes that exacerbate severe acute pancreatitis (SAP) and subsequent infection. Thymosin alpha 1 (Tα1) is an important immunomodulatory agent in clinical practice, but there is a lack evidence to prove its effectiveness in improving the condition of SAP patients. In this study, we aimed to evaluate the efficacy in meta-analysis.

Phenotypic drug discovery (PDD) involves screening compounds for their effects on cells, tissues, or whole organisms without necessarily understanding the underlying molecular targets. PDD differs from target-based strategies as it does not require knowledge of a specific drug target or its role in the disease. This approach can lead to the discovery of drugs with unexpected therapeutic effects or applications and allows for the identification of drugs based on their functional effects, rather than through a predefined target-based approach. Ultimately, disease definitions are mostly symptom-based rather than mechanism-based, and the therapeutics should be likewise. In recent years, there has been a renewed interest in PDD due to its potential to address the complexity of human diseases, including the holistic picture of multiple metabolites engaging with multiple targets constituting the central hub of the metabolic host-microbe interactions. Although PDD presents challenges such as hit validation and target deconvolution, significant achievements have been reached in the era of big data. This article explores the experiences of researchers testing the effect of a thymic peptide hormone, thymosin alpha-1, in preclinical and clinical settings and discuss how its therapeutic utility in the precision medicine era can be accommodated within the PDD framework.

This systematic review was conducted to assess the curative effect of Thymosin alpha 1 in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients. Six electronic databases including EMBASE, PubMed, Cochrane Library, China National Knowledge Infrastructure Database, Chinese Biomedical Database, and Wanfang Database were searched for eligible papers focusing on the thymosin alpha 1 treatment in AECOPD patients. The effectiveness outcomes included T cell subset, pulmonary function, arterial blood gases, and the length of hospital stay. Stata and Review Manager Software were used for data analysis. Thirty-nine randomised controlled trials with a total of 3,329 patients were included. Compared with the control treatment, Thymosin alpha 1 therapy significantly improved forced expiratory volume in 1 second [MD = 0.29, 95% (0.26, 0.32), p <0.001] and the ratio of forced expiratory volume in the first second to forced vital capacity [MD = 6.24, 95% (3.83, 8.65), p <0.001], increased the arterial partial pressure of oxygen [MD = 7.24, 95% (3.42, 11.07), p = 0.0002], lowered the arterial partial pressure of carbon dioxide [MD = -5.85, 95% (-9.38, -2.33), p = 0.001], shortened the length of hospital stay [MD = -5.39, 95% (-7.82, -2.97), p <0.001], raised the level of CD4+ T lymphocytes count [MD = 7.54, 95%(6.66, 8.41), p <0.001] and the ratio of CD4+/CD8+ [MD = 0.40, 95% (0.34, 0.46), p <0.001], and decreased level of CD8+ T lymphocytes count [MD = -2.74, 95% (-3.86, -1.63), p <0.001]. Thymosin alpha 1 could significantly boost the immune function, and improve pulmonary function and arterial blood gas of AECOPD patients than routine treatment only. More high-quality randomised controlled trials are needed to further confirm Thymosin alpha 1 efficacy. Key Words: Thymosin alpha 1, Efficacy, Acute exacerbation of chronic obstructive pulmonary disease, Meta-analysis.

The complex alterations of the immune system and the immune-mediated multiorgan injury plays a key role in host response to SARS-CoV-2 infection and in the pathogenesis of COVID-19, being also associated with adverse outcomes. Thymosin alpha 1 (Tα1) is one of the molecules used in the treatment of COVID-19, as it is known to restore the homeostasis of the immune system during infections and cancer. The use of Tα1 in COVID-19 patients had been widely used in China and in COVID-19 patients, it has been shown to decrease hospitalization rate, especially in those with greater disease severity, and reduce mortality by restoring lymphocytopenia and more specifically, depleted T cells. Persistent dysregulation with depletion of naive B and T cell subpopulations and expansion of memory T cells suggest a chronic stimulation of the immune response in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Our data obtained from an ex vivo study, showed that in PASC individuals with a chronically altered immune response, Tα1 improve the restoration of an appropriate response, most evident in those with more severe illness and who need respiratory support during acute phase, and in those with specific systemic and psychiatric symptoms of PASC, confirming Tα1 treatment being more effective in compromised patients. The results obtained, along with promising reports on recent trials on Tα1 administration in patients with COVID-19, offer new insights into intervention also for those patients with long-lasting inflammation with post-infectious symptoms, some of which have a delayed onset.

Thymosin α-1 (Tα-1) is an immunomodulating polypeptide of 28 amino acids, which was the first peptide isolated from thymic tissue and has been widely used for the treatment of viral infections, immunodeficiencies, and especially malignancies. Tα-1 stimulates both innate and adaptive immune responses, and its regulation of innate immune cells and adaptive immune cells varies under different disease conditions. Pleiotropic regulation of immune cells by Tα-1 depends on activation of Toll-like receptors and its downstream signaling pathways in various immune microenvironments. For treatment of malignancies, the combination of Tα-1 and chemotherapy has a strong synergistic effect by enhancing the anti-tumor immune response. On the basis of the pleiotropic effect of Tα-1 on immune cells and the promising results of preclinical studies, Tα-1 may be a favorable immunomodulator to enhance the curative effect and decrease immune-related adverse events of immune checkpoint inhibitors to develop novel cancer therapies.

Effort to search for the optimal COVID-19 treatment has continuously been attempted. Thymosin alpha-1 have immunomodulatory properties which may be beneficial in case of viral infection. This study's goal is to determine whether thymosin alpha-1 is effective in treating people with moderate-to-severe COVID-19.

Thymosin alpha 1 (Tα1) is a highly conserved 28 amino-acid peptide naturally occurring in the thymus and plays critical roles in T cell maturity and differentiation. Its synthetic form, thymalfasin, has been approved by various regulatory agencies in the treatment of hepatitis B viral infection and as an enhancer of vaccine response in immune-compromised populations. In China, it has also widely utilized in patients with cancer and severe infections, as well as the emergency use during (Severe Acute Respiratory Syndrome)SARS and COVID-19 pandemic as an immune-regulator. Recent studies showed that Tα1 could significantly improve overall survival (OS) in patients with surgically resectable non-small cell lung cancer (NSCLC) and liver cancers in the adjuvant setting. For patients with locally advanced, unresectable NSCLC, Tα1 could significantly reduce chemoradiation-induced lymphopenia, pneumonia, and trending improvement of OS. Preclinical evidence are emerging to demonstrate that Tα1 may augment efficacy of cancer chemotherapy by reversing efferocytosis-induced M2 polarization of macrophages via activation of a TLR7/SHIP1 axis and enhancing anti-tumor immunity by turning "cold-tumors" to "hot-tumors"; a protective role in reducing colitis caused by immune check-point inhibitors (ICIs). Potential enhancement of ICIs' clinical efficacies has also been indicated. ICIs have transformed ways treating patients with cancer but limitations such as relatively low response rates and certain safety issues remains. Given the roles of Tα1 in regulating cellular immunities and exceptional safety profiles demonstrated in decades clinical uses, we believe that it is plausible to explore implications of Tα1 the immune-oncology setting by combining with ICI-based therapeutic strategies. Background Activities of Tα1. Tα1 is a biological response modifier which activates various cells in the immune system [1-3]. Tα1 is therefore expected to have clinical benefits in disorders where immune responses are impaired or ineffective. These disorders include acute and chronic infections, cancers, and vaccine non-responsiveness. In severe sepsis, for example, sepsis-induced immunosuppression is increasingly recognized as the overriding immune dysfunction in these vulnerable patients [4] and there is now agreement that many patients with severe sepsis survive the first critical hours of the syndrome but eventually die later due to patients' immunosuppression which make the system difficulty to fight the primary bacterial infection, decreased resistance to secondary nosocomial infections, and reactivation of viral infections [5]. Tα1 has been shown to restore immune functions and help to reduce mortality in patients with severe sepsis.

The immunologic effects of chemotherapy-induced tumor cell death are not completely understood. Accumulating evidence suggests that phagocytic clearance of apoptotic tumor cells, also known as efferocytosis, is an immunologically silent process, thus maintaining an immunosuppressive tumor microenvironment (TME). Here we report that, in the breast tumor microenvironment, thymosin α-1 (Tα-1) significantly reverses M2 polarization of IL10-producing tumor-associated macrophages (TAM) during efferocytosis induced by apoptotic cells. Mechanistically, Tα-1, which bound to phosphatidylserine on the surface of apoptotic tumor cells and was internalized by macrophages, triggered the activation of SH2-containing inositol 5'-phosphatase 1 (SHIP1) through the lysosomal Toll-like receptor 7 (TLR7)/MyD88 pathway, subsequently resulting in dephosphorylation of efferocytosis-activated TBK1 and reduction of efferocytosis-induced IL10. Tα-1 combined with epirubicin chemotherapy markedly suppressed tumor growth in an in vivo breast cancer model by reducing macrophage-derived IL10 and enhancing the number and function of tumor-infiltrating CD4+ and CD8+ T cells. In conclusion, Tα-1 improved the curative effect of chemotherapy by reversing M2 polarization of efferocytosis-activated macrophages, suggesting that Tα-1 injection immediately after chemotherapy may contribute to highly synergistic antitumor effects in patients with breast cancer.

To evaluate the effect of thymosin alpha 1 on the prognosis of patients with coronavirus disease 2019 (COVID-19).

Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.

Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is the most frequent mutation causing cystic fibrosis (CF). F508del-CFTR is misfolded and prematurely degraded. Recently thymosin a-1 (Tα-1) was proposed as a single molecule-based therapy for CF, improving both F508del-CFTR maturation and function by restoring defective autophagy. However, three independent laboratories failed to reproduce these results. Lack of reproducibility has been ascribed by the authors of the original paper to the use of DMSO and to improper handling. Here, we address these potential issues by demonstrating that Tα-1 changes induced by DMSO are fully reversible and that Tα-1 peptides prepared from different stock solutions have equivalent biological activity. Considering the negative results here reported, six independent laboratories failed to demonstrate F508del-CFTR correction by Tα-1. This study also calls into question the autophagy modulator cysteamine, since no rescue of mutant CFTR function was detected following treatment with cysteamine, while deleterious effects were observed when bronchial epithelia were exposed to cysteamine plus the antioxidant food supplement EGCG. Although these studies do not exclude the possibility of beneficial immunomodulatory effects of thymosin α-1, they do not support its utility as a corrector of F508del-CFTR.

Thymosin alpha 1 (Ta1) is a natural occurring peptide hormone that is crucial for the maintenance of the organism homeostasis. It has been chemically synthesized and used in diseases where the immune system is hindered or malfunctioning.

Sepsis is a life-threatening organ dysfunction caused by host immune response to infection. In this regard, modifying host immune response may help to eliminate systemic infection and restore organ function. Thymosin alpha 1 (Tα1), acting as an immune modulator, exerts great biological influence in activating and restoring the dysregulated immune response for patients with sepsis.

In spite of the consistent benefits for HIV-1 infected patients undergoing antiretroviral therapy, a complete immune reconstitution is usually not achieved. Actually, antiretroviral therapy may be frequently accompanied by immunological unresponsiveness, persistent inflammatory conditions and inefficient cytotoxic T-cell response. Thymosin alpha 1 is a thymic peptide that demonstrates a peculiar ability to restore immune system homeostasis in different physiological and pathological conditions (i.e., infections, cancer, immunodeficiency, vaccination and aging) acting as multitasking protein depending on the host state of inflammation or immune dysfunction. This review reports the present knowledge on the in vitro and in vivo studies concerning the use of thymosin alpha 1 in HIV-1 infection. Recent findings and future perspectives of therapeutic intervention are discussed.

Thymosin alpha 1 (Ta1) is a peptide originally isolated from thymic tissue as the compound responsible for restoring immune function to thymectomized mice. Ta1 has a pleiotropic mechanism of action, affecting multiple immune cell subsets that are involved in immune suppression. Ta1 acts through Toll-like receptors in both myeloid and plasmacytoid dendritic cells, leading to activation and stimulation of signaling pathways and initiation of production of immune-related cytokines. Due to the immune stimulating effects of Ta1, the compound would be expected to show utility for treatment of immune suppression, whether related to aging or to diseases such as infection or cancer. Extensive studies in both the preclinical and clinical setting will be summarized in the subsequent sections. These studies have demonstrated improvements in immune system cell subsets and the potential of Ta1 for the treatment of a range of diseases.

Stimulating a successful host immune response may be a promising helpful therapy to achieve elimination of hepatitis B virus (HBV) infection in chronic hepatitis B (CHB). Thymosin α-1 (Tα-1), as an immunomodulatory agent, can enhance T-cell response in CHB patients and has been widely studied either alone or in combination with nucleos(t)ide analogs. This editorial reviews these articles to present the efficacy of Tα-1 in CHB.

Thymosin α 1 (Tα1) is a peptidic biological response modifier, which plays a significant role in activating and regulating various cells of the immune system. For the above-mentioned activities it is expected to exert a clinical benefit in the treatment of diseases where the immune system is altered.