Anionic phospholipid surfaces (aPL)

Anionic phospholipid surfaces, characterized primarily by the exposure of phosphatidylserine (PS), represent a unique therapeutic target due to their asymmetric distribution in healthy versus diseased cells. In normal physiological conditions, anionic phospholipids are strictly sequestered in the inner leaflet of the plasma membrane by ATP-dependent enzymes called flippases (Thorpe, 2010, PubMed: 20603233). However, in response to cellular stress, viral infection, or malignant transformation, this asymmetry is lost, leading to the externalization of PS on the outer cell surface. This exposure serves as a potent 'eat-me' signal for phagocytes and creates an immunosuppressive environment that allows tumors and viruses to evade the immune system (Pereira et al., 2014, PubMed: 24443831). Therapeutic agents targeting these surfaces, such as the monoclonal antibody bavituximab, are designed to bind specifically to these exposed lipids and redirect the immune response toward the diseased tissue. By blocking the immunosuppressive signaling of anionic phospholipids, these drugs can enhance the activity of T-cells and other immune effectors within the tumor microenvironment (Gerber et al., 2015, PubMed: 26159615). Furthermore, because anionic phospholipids are also exposed on the surface of many enveloped viruses and virally infected cells, they serve as a broad-spectrum target for antiviral therapies (Soares et al., 2008, PubMed: 18485918). This targeting strategy is particularly attractive in oncology and infectious disease because it focuses on a fundamental membrane change common to many pathologies rather than a specific protein mutation.

Other names

Negatively charged phospholipidsAcidic phospholipidsExternalized phosphatidylserinePhosphatidylserine-rich membranes

Binding to externalized anionic phospholipids (primarily phosphatidylserine) on the outer leaflet of the plasma membrane to induce antibody-dependent cellular cytotoxicity (ADCC), reverse immunosuppression in the tumor microenvironment, or inhibit viral entry and replication.