Thymosin Alpha-1

Thymosin α1 improves the outcomes of patients with hepatitis B virus-related acute-on-chronic liver failure by restoring immune balance.

Zhi-Hui Li, Li-Li Wu, Yuan-Qiang Zhu +8 more

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.

Thymosin α1-induced secretion of the IL-15/RA complex by THP-1-derived dendritic cells restrains HIV latency in vitro.

Chaoyu Chen, Jingna Xun, Jiangrong Wang +8 more

Viral reservoir presents a significant challenge in HIV-1 cure. We previously observed that Thymosin α1 (Tα1) may restrict the reservoir through the IL-15 pathway. However, the precise mechanism remains to be fully elucidated. Peripheral blood mononuclear cells (PBMCs) were obtained from people living with HIV-1 (PLWH). In vitro, THP-1 cells were differentiated into mature monocyte-derived dendritic cells (MoDCs) and co-cultured with PBMCs under various conditions. Intracellular HIV-1 p24 levels, CD8+ T and NK cell functionality, and reservoir size were evaluated. In vitro, Tα1 stimulation of MoDCs resulted in significant immune response and secretion of IL-15/RA complex (p < 0.001). This interaction with IL-2 Rβ/γ receptors on T cells enhanced the intracellular secretion of CCL3/5, IFN-γ, and TNF-α in CD8+ T cells (p < 0.05), which inhibited p24 levels in CD4+ T cells (p = 0.002), and reduced HIV-1 integrated DNA levels (p = 0.012). Furthermore, the secretion levels of IFN-γ, TNF-α, and GZMB in NK cells and proportion of CD8+ TVM cells significantly increased following co-culture. These alterations were found to be markedly inversely associated with reservoir size and reactivation. However, these effects were observed in PBMCs from immunological responders (CD4+ T cell count > 350 cells/µL) rather than nonresponders. Tα1 enhances CD8+ T cell function, promotes TVM proliferation, and suppresses reservoir size and reactivation via IL-15 pathway activation in dendritic cells, which warrants testing in functional cure trials in the future.

A multipronged Tα1 reset of CD8+ T cell cytotoxicity against breast cancer.

Smriti Mishra, Gaurang Telang, Anurag Sureshbabu +4 more

Thymosin α1 (Tα1) is an endogenous thymic peptide that enhances immune competence through activation of T cells, dendritic cells, and innate immune pathways. However, its direct impact on CD8+ T cell-mediated antitumor immunity in breast cancer remains unclear. In this study, CD8+ T cells isolated from peripheral blood of ten healthy donors were cultured under unstimulated, CD3/CD28-stimulated, Tα1-treated, or exhaustion-rescue conditions to evaluate cytotoxic activity against MDA-MB-231 breast cancer cells and CD44+ cancer stem-like cells (CD44+ CSC-like cells). Tα1 significantly enhanced CD8+ T cell-mediated apoptosis, suppressed tumor cell proliferation, and increased granzyme B secretion beyond CD3/CD28 stimulation alone. In exhausted T cells, Tα1 partially restored effector function and reduced PD-1, TIM-3, and LAG-3 expression. Complementary transcriptomic analysis using a compact four-gene Tα1 Response Index (Tα1-RI: TLR9, TLR2, IRF1, NLRC5) in TCGA-BRCA (n = 1,112) confirmed positive correlations with antigen presentation and cytotoxic programs and enrichment in CD8-like T cells in single-cell datasets. Collectively, these findings demonstrate that Tα1 enhances CD8+ T cell cytotoxicity while alleviating exhaustion, supporting its potential as an adjunct immunomodulator for improving immune surveillance in breast cancer.

Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial.

Hao Xu, Fengyuan Li, Bowen Li +8 more

Neoadjuvant immunochemotherapy has emerged as a promising strategy for locally advanced gastric and gastroesophageal junction (G/EGJ) adenocarcinoma, but a substantial proportion of patients derive limited benefit. Thymalfasin is an immunomodulatory peptide that may amplify antitumor immunity while attenuating toxicity. We conducted a phase II trial to evaluate anti-PD-1 plus SOX (S-1 and oxaliplatin) immunochemotherapy combined with thymalfasin as neoadjuvant treatment for G/EGJ adenocarcinoma.

Thymosin α1 Combined With 2HRZE/4HR Regimen as a Potential Treatment of Pulmonary Tuberculosis: An Analysis of Immune Function, Pulmonary Function and Inflammatory Response.

Guofeng Wu, Xuelian Sun

Aims/Background Immunotherapy plays a critical role in the clinical treatment of tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, in which immune damage promotes the occurrence and development of the disease. This study aimed to investigate the efficacy of thymosin α1 combined with the 2HRZE/4HR (2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by 4 months of isoniazid and rifampin) in the treatment of pulmonary tuberculosis and its effect on immune function and inflammatory factors. Methods A retrospective analysis was conducted on 106 pulmonary tuberculosis patients treated between October 2022 and June 2024. The patients were divided into two groups based on their treatment regimens: the control group (n = 47) received the 2HRZE/4HR treatment, while the observation group (n = 59) received thymosin α1 in addition to the 2HRZE/4HR treatment. All patients underwent a 6-month treatment course. Clinical efficacy was evaluated 6 months after treatment based on clinical symptoms and sputum smear results. The study compared foci resorption rates, cavity closure rates, and changes in pulmonary function indices, immune function indices, and inflammatory factor levels before and after treatment between the two groups. Adverse reactions were also recorded and analyzed. Results The total effective rate and the rate of foci resorption and cavity closure of the observation group were higher than the control group (p < 0.05). After 6 months of treatment, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and peak expiratory flow (PEF) of the observation group were higher compared to the control group (p < 0.05). Compared with the control group, the observation group exhibited lower mRNA expression of T-cell immunoglobulin mucin-1 (TIM-1) and TIM-3; reduced levels of immunoglobulin E (IgE), sputum supernatant, serum interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α); but higher interferon-gamma (IFN-γ) levels (p < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). Conclusion Thymosin α1 combined with the 2HRZE/4HR regimen holds promise as an effective treatment of pulmonary tuberculosis by improving immune function and pulmonary function of patients while attenuating the inflammatory response.

Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.

Bin Gu, Yu Zhou, Yao Nie +8 more

Despite advances in understanding sepsis pathophysiology and extensive research, few treatments effectively target its underlying immune dysfunction. Thymosin α1 (Tα1) shows promise as an immunomodulator, but its impact on sepsis remains unclear.

Thymosin alpha 1 alleviates inflammation and prevents infection in patients with severe acute pancreatitis through immune regulation: a systematic review and meta-analysis.

Yong Tian, Jiaqi Yao, Yihan Ma +4 more

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.

The Synergistic and Attenuated Mechanism of Action of the Xihuang Pill in Dual Immunotherapy After Stenting for Advanced Cholangiocarcinoma: A Controlled Clinical Trial.

Peng Wang, Yu-Huan Wang, Yun Tao +2 more

This study aims to investigate the synergistic and attenuation mechanism of Xihuang pill in the treatment of cholangiocarcinoma (CCA), thereby providing a reliable scientific basis for the selection of postoperative treatment strategies in cholangiocarcinoma patients.

Effect of thymosin α1 on Immune response and organ function in acute aortic dissection surgery: PANDA II trial protocol.

Hong Liu, Si-Chong Qian, Ying-Yuan Zhang +16 more

This multicenter randomized controlled trial evaluates the efficacy of thymosin alpha 1 (Tα1) supplementation in preventing organ dysfunction following acute type A aortic dissection (ATAAD) repair. Over 330 patients will be equally assigned to receive either Tα1 plus standard care or placebo with standard management. The primary endpoint involves calculating the difference in mean postoperative Sequential Organ Failure Assessment (SOFA) scores between groups, measured daily from postoperative days 7. By targeting post-operative immune system imbalance, this study aims to establish a novel therapeutic approach for reducing systemic inflammatory response syndrome (SIRS)-mediated organ injury and improving long-term outcomes in this high-risk population. Results will be disseminated through peer-reviewed publications and international conferences.Trial registration: ClinicalTrials.gov Registry (NCT05339529).

Effect analysis of entecavir on serum hyaluronic acid, laminin and IV collagen in the treatment of hepatitis B E-antigen-positive chronic hepatitis B.

Jiancheng Qian, Xiaoyong Sun, Yue Cheng

To observe and analyse the clinical effects of entecavir on serum hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) in patients with hepatitis B e-antigen (HBeAG)-positive chronic hepatitis B during clinical treatment.

Hypofractionated radiotherapy combined with a PD-1 inhibitor, granulocyte macrophage-colony stimulating factor, and thymosin-α1 in advanced metastatic solid tumors: a multicenter Phase II clinical trial.

Jiamin Yu, Li Yin, Wenjie Guo +13 more

This multicenter Phase II clinical study assessed the efficacy and safety of hypofractionated radiotherapy (HFRT) in combination with a PD-1 inhibitor, granulocyte macrophage-colony stimulating factor (GM-CSF), and thymosin-α1 in patients with heavily treated metastatic solid tumors.

Indications for an antidepressive effect of thymosin alpha-1 in a small open-label proof of concept study in common variable immune deficiency patients with depression.

Daniël G Aynekulu Mersha, Sarah E Fromme, Frank van Boven +7 more

A considerable proportion (21%) of patients with common variable immunodeficiency (CVID) suffers from depression. These subjects are characterized by reduced naïve T cells and a premature T cell senescence similar to that of patients with major depressive disorder (MDD). It is known that T cells are essential for limbic system development/function. Treatment with thymosin α1 (Tα1) is capable to increase the thymus output of naïve T cells.

Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Ailing Cao, Fanchao Feng, Xianmei Zhou

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.

A Prospective and Randomized Control Study on Effects of Thymalfasin for Injection on Perioperative Immune Function and Long-term Prognosis of Patients with Colorectal Cancer.

Wenbo Niu, Zhiying Li, Zhihan Li +5 more

The objective of this study is to explore the effects of thymalfasin for injection on perioperative immune function and long-term prognosis of patients with colorectal cancer (CRC). In total, 400 patients who entered the groups from February 2019 to January 2021 and underwent radical resection of CRC in the Fourth Hospital of Hebei Medical University were the study subjects. They were separated into experimental group (0-199, XELOX chemotherapy and thymalfasin for injection) and control group (200-400, XELOX chemotherapy) by random number table, and the experimental group was randomly divided into conventional-dose group (n = 100, 1.6 mg of thymalfasin for injection, twice a week) and high-dose group (n = 100, 1.6 mg of thymalfasin for injection, thrice a week) according to a ratio of 1:1, to analyze the effects of different treatment schemes on perioperative immune function and long-term prognosis of CRC patients. Compared with control group, the conventional-dose group and high-dose group had notably lower incidences of perioperative infection (P < 0.05), with no significant difference in both groups (P > 0.05). The experimental group had significantly lower overall incidence of early and late postoperative complications, local recurrence rate and the incidence of distant metastasis, and higher perioperative immune function indexes and median disease free survival (DFS) (P < 0.05).         The conventional-dose and high-dose thymalfasin for injection effectively improves the perioperative immune function of CRC patients and reduces the incidence of postoperative complications, as an effective treatment for such patients, which can benefit patients.

Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy.

Kua Liu, Lingkai Kong, Huawei Cui +9 more

Although oncolytic adenoviruses are widely studied for their direct oncolytic activity and immunomodulatory role in cancer immunotherapy, the immunosuppressive feedback loop induced by oncolytic adenoviruses remains to be studied. Here, we demonstrate that type V adenovirus (ADV) induces the polarization of tumor-associated macrophages (TAMs) to the M2 phenotype and increases the infiltration of regulatory T cells (Tregs) in the tumor microenvironment (TME). By selectively compensating for these deficiencies, thymosin alpha 1 (Tα1) reprograms "M2-like" TAMs toward an antitumoral phenotype, thereby reprogramming the TME into a state more beneficial for antitumor immunity. Moreover, ADVTα1 is constructed by harnessing the merits of all the components for the aforementioned combinatorial therapy. Both exogenously supplied and adenovirus-produced Tα1 orchestrate TAM reprogramming and enhance the antitumor efficacy of ADV via CD8+ T cells, showing promising prospects for clinical translation. Our findings provide inspiration for improving oncolytic adenovirus combination therapy and designing oncolytic engineered adenoviruses.

Immune-Enhancing Treatment among Acute Necrotizing Pancreatitis Patients with Metabolic Abnormalities: A Post Hoc Analysis of a Randomized Clinical Trial.

Xiaofei Huang, Wenjian Mao, Xingxing Hu +8 more

Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immune-enhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients.

PD-1 inhibitor combined with SBRT, GM-CSF, and thymosin alpha-1 in metastatic breast cancer: A case report and literature review.

Jiamin Yu, Qiang Wang, Lijun Wang +2 more

Triple-negative breast cancer is characterized by a worse prognosis compared with other breast cancer subtypes, especially in the case of pretreated metastatic triple-negative breast cancer (mTNBC). Because of the limited treatment options and suboptimal response rates, there is a pressing need to explore novel treatment protocols.

Evaluation of the efficacy and safety of a precise thymalfasin-regulated PRaG regimen for advanced refractory solid tumours: protocol for the open-label, prospective, multicentre study (PRaG5.0 study).

Yuehong Kong, Rongzheng Chen, Meiling Xu +11 more

The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients.

Comprehensive Review of the Safety and Efficacy of Thymosin Alpha 1 in Human Clinical Trials.

Elliot Dinetz, Edwin Lee

This study aims to assess the safety and efficacy of Thymosin Alpha 1 (Tα1) through a comprehensive narrative review of clinical studies involving over 11 000 human subjects in more than 30 trials. The focus was on Tα1's application in COVID-19, autoimmune conditions, and cancer treatment, with implications for future considerations.

Therapeutic applications of thymosin peptides: a patent landscape 2018-present.

Michael Quagliata, Anna Maria Papini, Paolo Rovero

Thymosins are small proteins found mainly in the thymus. They are involved in several biological processes, including immunoregulation, angiogenesis, and anti-inflammatory activity. Due to these multiple activities, thymosins are widely used as therapeutics. In fact, these peptides have shown interesting results in the treatment of eye disorders, anticancer therapy, and dysregulated immune disorders.

Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection.

M S Espinar-Buitrago, E Vazquez-Alejo, E Magro-Lopez +3 more

Tα1 (Thymosin-alpha-1) is a thymus-derived hormone that has been demonstrated to be effective on diverse immune cell subsets. The objective of this study was to determine the in vitro immunomodulatory effect of Tα1 in human cytomegalovirus (HCMV) infection. Dendritic cells (DCs) were isolated from peripheral blood mononuclear cells (PBMCs) by negative selection and cultured in the presence or absence of Tα1. The immunophenotyping of DCs was characterised by multiparametric flow cytometry assessing CD40, CD80, TIM-3 and PDL-1 markers, as well as intracellular TNFα production. Then, autologous CD4+ or CD8+ T-Lymphocytes (TLs) isolated by negative selection from PBMCs were co-cultured with DCs previously treated with Tα1 in the presence or absence of HCMV. Intracellular TNFα, IFNγ, IL-2 production, CD40-L and PD-1 expression were assessed through immunophenotyping, and polyfunctionality in total TLs and memory subsets were evaluated. The results showed that Tα1 increased CD40, CD80, TIM-3 and TNFα intracellular production while decreasing PDL-1 expression, particularly on plasmacytoid dendritic cells (pDCs). Therefore, Tα1 modulated the production of TNFα, IFNγ and IL-2 in both total and memory subsets of CD4+ and CD8+ TLs by upregulating CD40/CD40-L and downregulating PDL-1/PD-1 expression. Our study concludes that Tα1 enhances antigen-presenting capacity of DCs, improves TLs responses to HCMV infection, and enhances the polyfunctionality of CD8+ TLs. Consequently, Tα1 could be an alternative adjuvant for use in therapeutic cell therapy for immunocompromised patients.

Thymalfasin therapy accelerates COVID-19 pneumonia rehabilitation through anti-inflammatory mechanisms.

Zirui Wang, Cong Wang, Xiaohua Fei +3 more

Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital.

Thymosin α1 modulated the immune landscape of COVID-19 patients revealed by single-cell RNA and TCR sequencing.

Han Bai, Liyuan Liang, Xin Qi +9 more

The Coronavirus disease-19 (COVID-19) pandemic has posed a serious threat to global health. Thymosin α1 (Tα1) was considered to be applied in COVID-19 therapy. However, the data remains limited.

Zoledronic acid and thymosin α1 elicit antitumor immunity against prostate cancer by enhancing tumor inflammation and cytotoxic T cells.

Sheng Wang, Maohua Huang, Minfeng Chen +7 more

Advanced or metastatic prostate cancer (PCa) is still an incurable malignancy with high lethality and a poor prognosis. Despite the remarkable success of immunotherapy against many types of cancer, most patients with PCa receive minimal benefit from current immunotherapeutic strategies, because PCa is an immune cold tumor with scarce T-cell infiltration in the tumor microenvironment. The aim of this study was to develop an effective immunotherapeutic approach for immune cold PCa tumors.

Reduced numbers of naïve CD4 + T cells and an altered CD4/CD8 balance in depressed common variable immune deficiency (CVID) patients. Is thymosin-α1 a possible treatment?

Olivia Manusama, Sajni Singh, Rik A Brooimans +4 more

In the 1990's the macrophage-T-cell-theory of depression was posed stating that low grade inflammation and an abnormal T cell system destabilize the development and function of the emotional brain in such a way, that individuals become ultrasensitive to stress. Recently we gathered evidence that indeed higher frequencies of CD4+ memory T cells, lower frequencies of naive CD4 + T cells, higher frequencies of CD8 + T cells (the latter two in part elicited by Cytomegalovirus, CMV, infection) are a characteristic of Major Depressive Disorder (MDD). In MDD patients with a history of childhood trauma and severe depression monocytes are inflammatory activated. Low grade inflammation and T cell system defects have also been reported in patients with Common Variable Immune Deficiency (CVID) (next to antibody production defects). CVID patients show a higher prevalence of mild depression. The aim of this study was to determine T cell frequencies and monocyte inflammatory activation in CVID patients with and without depression. This study confirms that CVID patients have CMV independent decreases in the frequency of naïve CD4 + T cells and it de novo shows a CMV dependent increase in the expression of inflammatory genes in monocytes. CVID patients with depression are additionally characterized by a CMV independent increase in the frequency of naïve CD8 + T cells, while lacking monocyte inflammatory activation. In conclusion, depressed CVID patients have T cell abnormalities comparable to that of patients with regular MDD. These abnormalities are presently targeted by thymosin α1 in an open-label proof of concept trial.

Thymosin α1 and Its Role in Viral Infectious Diseases: The Mechanism and Clinical Application.

Nana Tao, Xie Xu, Yuyuan Ying +4 more

Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS). Tα1 can influence the functions of immune cells, such as T cells, B cells, macrophages, and natural killer cells, by interacting with various Toll-like receptors (TLRs). Generally, Tα1 can bind to TLR3/4/9 and activate downstream IRF3 and NF-κB signal pathways, thus promoting the proliferation and activation of target immune cells. Moreover, TLR2 and TLR7 are also associated with Tα1. TLR2/NF-κB, TLR2/p38MAPK, or TLR7/MyD88 signaling pathways are activated by Tα1 to promote the production of various cytokines, thereby enhancing the innate and adaptive immune responses. At present, there are many reports on the clinical application and pharmacological research of Tα1, but there is no systematic review to analyze its exact clinical efficacy in these viral infectious diseases via its modulation of immune function. This review offers an overview and discussion of the characteristics of Tα1, its immunomodulatory properties, the molecular mechanisms underlying its therapeutic effects, and its clinical applications in antiviral therapy.

Thymosin α1 interacts with Galectin-1 modulating the β-galactosides affinity and inducing alteration in the biological activity.

Claudia Matteucci, Ridvan Nepravishta, Ayele Argaw-Denboba +8 more

The study of mechanism of action of Thymosin alpha 1 (Tα1) and the basis of the pleiotropic effect in health and disease, is one of the main focus of our ongoing research. Tα1 is a thymic peptide that demonstrates a peculiar ability to restore 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. However, few are the information about mechanisms of action mediated by specific Tα1-target protein interaction that could explain its pleiotropic effect. We investigated the interaction of Tα1 with Galectin-1 (Gal-1), a protein belonging to an oligosaccharide binding protein family involved in a variety of biological and pathological processes, including immunoregulation, infections, cancer progression and aggressiveness. Using molecular and cellular methodological approaches, we demonstrated the interaction between these two proteins. Tα1 specifically inhibited the hemagglutination activity of Gal-1, the Gal-1 dependent in vitro formation of endothelial cell tubular structures, and the migration of cancer cells in wound healing assay. Physico-chemical methods revealed the details of the molecular interaction of Tα1 with Gal-1. Hence, the study allowed the identification of the not known until now specific interaction between Tα1 and Gal-1, and unraveled a novel mechanism of action of Tα1 that could support understanding of its pleiotropic activity.

Thymosin alpha 1 restores the immune homeostasis in lymphocytes during Post-Acute sequelae of SARS-CoV-2 infection.

Antonella Minutolo, Vita Petrone, Marialaura Fanelli +16 more

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.