Tilos Therapeutics is developing antibody therapeutics specific for LAP, latency-associated peptide of TGFβ. Anti-LAP antibodies effectively reduce tumor growth in mouse cancer models and have the potential to be a powerful new class of therapeutics in the treatment of cancer, as well as fibrosis and autoimmunity.
Anti-LAP antibodies modify the tumor microenvironment via two distinct pathways.
1. Depleting LAP+ inhibitory cells
LAP expression defines cells that use TGFβ as part of their inhibitory toolbox: regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Anti-LAP antibody treatment depletes these cells from the tumor microenvironment and frees the innate and adaptive immune responses to effectively clear the tumor.
2. Inhibiting TGFβ release
LAP is a protein cage that holds TGFβ in a latent state. Anti-LAP antibodies stabilize the LAP-TGFβ complex and prevent release of the active cytokine. Reducing TGFβ levels leads to broad effects on tumor growth, reducing metastasis, immunosuppression, epithelial-to-mesenchymal transition and angiogenesis.
Tilos has a pipeline of anti-LAP antibodies that deplete specific inhibitory cell populations and modulate the release of active TGFβ in specific cellular niches. Tilos’s anti-LAP antibodies have significant potential in the treatment of cancer, as well as fibrosis and autoimmune disease.