Human MS4A1 Virus-Like Particles

MS4A1, also known as CD20, is a cell surface protein primarily expressed on B lymphocytes and plays a key role in immune system regulation. This non-glycosylated phosphoprotein spans the cell membrane four times, forming a tetraspanin-like structure that regulates calcium flux and B cell activation. MS4A1 is a key biomarker for B cell malignancies, such as non-Hodgkin''s lymphoma and chronic lymphocytic leukemia, making it a prime target for therapeutic intervention. Monoclonal antibodies such as rituximab and obinutuzumab specifically bind to MS4A1, triggering antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC), leading to the elimination of malignant B cells. Beyond oncology, MS4A1 has also been implicated in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

MS4A1 virus-like particles (VLPs) are engineered nanostructures that mimic the native conformation of MS4A1 on a viral particle scaffold but do not carry infectious genetic material. These VLPs are produced by expressing MS4A1 and viral structural proteins (such as HIV Gag or the capsid protein of hepatitis B virus) in heterologous systems such as mammalian, insect, or yeast cells. The self-assembly properties of these proteins allow them to form non-infectious particles with MS4A1 densely packed on their surface, retaining its native tertiary structure and antigenicity. MS4A1 VLPs are powerful tools for immunotherapy, vaccine development, and diagnostic assays. For example, they can be used to generate high-affinity antibodies against MS4A1 for research or clinical applications or as baits to study B cell receptor interactions. In cancer vaccines, MS4A1 VLPs may stimulate a robust immune response by presenting the antigen in a highly immunogenic format, potentially overcoming tolerance mechanisms in B cell malignancies.