CD20directed

CD20-directed refers to therapies that target CD20, a transmembrane protein broadly expressed on mature B cells but not on hematopoietic stem cells or plasma cells. These therapies are used to treat certain B-cell malignancies and some autoimmune diseases by depleting B cells that express CD20.

Mechanism of action involves binding to CD20 on the cell surface, which triggers B-cell depletion through several pathways, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). Some agents may also induce direct signaling leading to apoptosis. CD20-directed antibodies are typically given by intravenous infusion and may require premedication to reduce infusion-related reactions.

Prominent examples include rituximab (a chimeric IgG1 antibody), obinutuzumab (glycoengineered humanized IgG1), ofatumumab (fully human IgG1), ocrelizumab (humanized IgG1), and ublituximab (glycoengineered IgG1). These agents have been approved for a range of conditions, notably non-Hodgkin lymphomas, chronic lymphocytic leukemia, and autoimmune diseases such as rheumatoid arthritis. Ocrelizumab is also approved for multiple sclerosis. Dosing and treatment schedules vary by agent and indication.

Adverse effects include infusion reactions, increased risk of infections due to B-cell depletion, hypogammaglobulinemia with prolonged use, and rare but serious events such as reactivation of hepatitis B and progressive multifocal leukoencephalopathy (PML). Resistance or relapse can occur through loss or downregulation of CD20 expression on B cells, among other mechanisms.

Ongoing research aims to optimize efficacy, reduce toxicity, and expand indications, including combination regimens and next-generation anti-CD20 antibodies.