Thymosin alpha-1

Mechanism (as reported)

Across the provided sources, Tα-1 is described as modulating immune responses, including augmenting T-cell function and impacting innate and adaptive immune cells. One mechanistic cancer study reported that Tα-1 bound phosphatidylserine on apoptotic tumor cells and was internalized by macrophages, triggering a TLR7/MyD88 pathway and activation of SHIP1, leading to dephosphorylation of TBK1 and reduced efferocytosis-induced IL10. (PMIDs: 30063866, 11381492, 35364609, 36812669)

Key findings (each cites a source)

• A review of articles on chronic hepatitis B reported that Tα-1 monotherapy was effective in suppressing viral replication compared with untreated control or conventional interferon, and that combination therapy with Tα-1 plus lamivudine or IFN-α showed better HBV DNA suppression and HBeAg seroconversion; it also noted that clinical studies of Tα-1 combined with entecavir on HBV-cirrhosis are ongoing. [PMID 25640173]
• A cancer-focused review described thymosin α-1 as an immunomodulating polypeptide that stimulates both innate and adaptive immune responses, with regulation described as involving Toll-like receptor activation and downstream signaling pathways in different immune microenvironments; it also described a reported synergy with chemotherapy in malignancies aimed at enhancing anti-tumor immune response and affecting immune checkpoint inhibitor-related immune adverse events in the context of the review. [PMID 36812669]
• A study reported that in the breast tumor microenvironment, Tα-1 significantly reversed M2 polarization of IL10-producing tumor-associated macrophages during efferocytosis, and mechanistically described involvement of a TLR7/MyD88 pathway leading to SHIP1 activation and reduction of efferocytosis-induced IL10; it also reported that Tα-1 combined with epirubicin suppressed tumor growth in an in vivo breast cancer model, associated with reduced macrophage-derived IL10 and enhanced tumor-infiltrating CD4+ and CD8+ T cells. [PMID 35364609]
• A general review described thymosin alpha-1 as a synthetic polypeptide, discussed pharmacology/pharmacokinetics/clinical efficacy and adverse effects, and summarized clinical efficacy evaluations in hepatitis B and hepatitis C, including that TA1 in hepatitis B had been evaluated in 195 patients across four clinical trials with reported HBV DNA clearance outcomes in multiple study settings compared with interferon and historical or untreated controls; it also described mixed results across chronic hepatitis B or C trial experiences and noted a tolerability profile characterized mainly by local irritation at the injection site in the reviewed material. [PMID 11381492]
• A review on aging reported that thymosin alpha-1 is discussed as an immunomodulatory peptide produced by the thymus, described as having anti-inflammatory and antioxidant properties, and stated that preclinical and clinical studies reported improvement of vaccine response in the elderly and mitigation of immunosenescence; it also discussed the hybrid drug Refnot (TNF-α fusion with Tα-1) as a research approach mentioned in that review. [PMID 41373628]
• A review on sepsis reported clinical studies of Tα-1 treatment alone and in combination with anti-inflammatory strategies, stating that previous studies reported reduced mortality, improved HLA-DR expression on monocytes, and diminished incidence of secondary infection; it also emphasized limitations including heterogeneity of sepsis and difficulty generalizing results, and suggested future trials might focus on immunosuppressed individuals. [PMID 30063866]
• A review on HIV-1 reported that thymosin alpha-1 is discussed as a thymic peptide with ability to restore immune system homeostasis across different physiological and pathological conditions, and it described that the review reports present knowledge on in vitro and in vivo studies of Tα-1 in HIV-1 infection and discusses therapeutic intervention perspectives. [PMID 28106477]
• A systematic review and meta-analysis reported that across 39 randomized controlled trials (3,329 patients) of Tα-1 plus routine treatment for acute exacerbation of COPD, compared with control treatment, Tα-1 therapy significantly improved several outcomes reported in the meta-analysis, including forced expiratory volume in 1 second, FEV1/FVC ratio, arterial oxygen and carbon dioxide measures, length of hospital stay, and CD4+/CD8+ T-cell related measures; it also stated that more high-quality randomized controlled trials are needed to further confirm Tα-1 efficacy. [PMID 39648386]