Transforming growth factor beta 1 (Latent TGF-β1) (Latent TGF-β1)

Latent Transforming Growth Factor beta 1 (Latent TGF-β1) is the inactive precursor complex of TGF-β1, a multifunctional cytokine that regulates immune responses, cell proliferation, and tissue repair. It consists of the mature TGF-β1 homodimer non-covalently associated with the Latency-Associated Peptide (LAP), which prevents the cytokine from binding to its receptors (UniProt P01137). This latent complex is often anchored to the extracellular matrix by Latent TGF-β Binding Proteins (LTBPs) or to the surface of regulatory T cells and platelets by GARP (LRRC32) (Hinz, 2015). Activation of the latent complex is a tightly regulated process often mediated by integrins (such as αvβ6 and αvβ8), which mechanically release the active TGF-β1 in response to tissue stress or injury (Martin et al., 2020). In pathological states, excessive activation of Latent TGF-β1 leads to organ fibrosis and promotes an immunosuppressive "cold" tumor microenvironment that helps cancers evade the immune system. Modern therapeutic approaches, such as the monoclonal antibody SRK-181, specifically target the latent form to prevent the release of active TGF-β1, offering a more selective and potentially safer profile than traditional pan-TGF-β inhibitors (Scholar Rock, 2023). By inhibiting the activation step rather than the active cytokine itself, these therapies aim to avoid the systemic toxicities, such as cardiac and epithelial issues, that have hindered previous TGF-β targeting strategies (AbbVie, 2024).

Other names

Pro-TGF-beta-1LAP-TGF-beta-1TGFB1Latency-associated peptide-TGF-beta-1 complexSmall latent complex (SLC)Large latent complex (LLC)

Selective inhibition of the activation of the latent TGF-β1 complex, preventing the release of the mature, active growth factor into the microenvironment.