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.

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Anti-LAP antibodies modify the tumor microenvironment via two distinct pathways. 

 

1. Depleting LAP+ inhibitory cells

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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

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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.

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