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]