AXL antibodies target the receptor tyrosine kinase AXL, a member of the TAM (TYRO3. AXL, MERTK) family. AXL is characterized by an extracellular ligand-binding domain with two immunoglobulin-like domains and two fibronectin type III repeats, coupled with an intracellular kinase domain. It binds its primary ligand, Gas6. to regulate cellular processes such as proliferation, survival, migration, and immune modulation. Dysregulation of AXL signaling is implicated in cancer progression, metastasis, and therapy resistance, particularly through epithelial-mesenchymal transition (EMT) and interactions with the tumor microenvironment. Overexpression of AXL is observed in various malignancies, including leukemia, breast, lung, and pancreatic cancers, correlating with poor prognosis.
AXL antibodies are developed for therapeutic and diagnostic purposes. Therapeutically, they block Gas6 binding or AXL dimerization, inhibiting downstream pathways like PI3K/AKT and MAPK, thereby suppressing tumor growth and enhancing chemotherapy sensitivity. Examples include monoclonal antibodies (e.g., Bemcitamab) and antibody-drug conjugates in preclinical or clinical trials. Additionally, AXL-targeting agents show potential in modulating immune responses, such as reducing immunosuppressive macrophages or dendritic cells in cancer. Diagnostically, AXL antibodies aid in detecting AXL expression levels in tumors, serving as biomarkers for patient stratification. Despite promising preclinical data, challenges remain, including resistance mechanisms and optimizing selectivity to minimize off-target effects. Ongoing research aims to expand AXL antibody applications in oncology and inflammatory diseases.