Antibodies are specialized Y-shaped proteins produced by the immune system to identify and neutralize foreign substances, known as antigens, that enter the body. These protective proteins circulate in the blood and tissues, acting like a lock and key to bind precisely to specific targets. Axl antibodies represent a particular class of these immune proteins, engineered to recognize and interact with a specific protein called the Axl receptor. Their development holds significant promise in scientific research, as they offer a targeted approach to understand and potentially influence various biological processes.
What is the Axl Receptor?
The Axl receptor, also known as AXL receptor tyrosine kinase, is a protein found on the surface of many cells throughout the body. It belongs to a family of receptors called TAM (Tyro3, Axl, Mer). Axl plays a role in cellular processes, including cell growth, survival, and migration.
Axl clears apoptotic (dying) cells and their debris, and helps regulate immune responses by dampening inflammatory signals. Its activation occurs when it binds to its ligand, Growth Arrest-Specific 6 (GAS6). This binding triggers a cascade of internal signals within the cell, influencing processes like cell proliferation, differentiation, and adhesion.
How Axl Antibodies Function
Axl antibodies bind to the Axl receptor, influencing its activity. One primary mechanism involves blocking the interaction between the Axl receptor and its ligand, GAS6. By binding to the extracellular domain of Axl, these antibodies prevent GAS6 from attaching, disrupting the signaling pathway. This inhibition can prevent the receptor from becoming active, thereby suppressing downstream cellular responses.
Axl antibodies can also mark cells expressing the Axl receptor for removal by the immune system. Once an antibody binds to its target on a cell surface, it acts as a flag, signaling other immune cells to identify and eliminate the cell. This mechanism can be harnessed to target cells where Axl activity is undesirable. The precise impact of antibody binding depends on the specific design of the Axl antibody and the cellular context.
Targeting Diseases with Axl Antibodies
Dysregulation of the Axl receptor is linked to the development and progression of various diseases. In cancers, Axl is often overexpressed and contributes to tumor cell survival, proliferation, migration, invasion, and resistance to therapies like chemotherapy and radiation. Axl activation can promote processes such as epithelial-mesenchymal transition (EMT), involved in metastasis, and can also suppress anti-tumor immune responses. Research is actively exploring how Axl antibodies can counteract these effects.
Beyond cancer, Axl’s dysregulation has also been implicated in fibrotic conditions. For instance, Axl contributes to liver fibrosis by increasing the activation of hepatic stellate cells, involved in scar tissue formation. In this context, Axl antibodies could potentially mitigate the progression of fibrosis by inhibiting these cellular activities.
Furthermore, Axl has been identified as a candidate receptor for certain viral infections, including SARS-CoV-2. Axl may facilitate the entry of these viruses into host cells. This connection opens avenues for investigating Axl antibodies as a strategy to block viral entry or reduce infection severity, representing a potential therapeutic approach for infectious diseases. Overall, the ability of Axl antibodies to modulate Axl activity makes them a promising area of research for addressing various diseases.