CD20 antibodies are monoclonal immunotherapies targeting the CD20 surface protein, a 33–37 kDa transmembrane phosphoprotein expressed on mature B cells but absent on hematopoietic stem cells and plasma cells . This specificity allows precise depletion of malignant B cells while preserving humoral immunity . First introduced in 1997 with rituximab, CD20 antibodies revolutionized treatment for B-cell malignancies (e.g., non-Hodgkin lymphoma, chronic lymphocytic leukemia) and autoimmune diseases .
CD20 antibodies exert therapeutic effects through three primary mechanisms:
Note: Fcγ receptor interactions are pivotal, as demonstrated by preclinical studies showing rituximab’s dependence on γ-chain-associated activatory FcγRs .
CD20 antibodies are cornerstone therapies for B-cell malignancies and autoimmune disorders:
Non-Hodgkin Lymphoma (B-NHL): Rituximab combined with chemotherapy (e.g., R-CHOP) significantly improves survival .
Chronic Lymphocytic Leukemia (CLL): Obinutuzumab (a next-generation anti-CD20 antibody) shows superior progression-free survival (PFS) compared to rituximab in first-line treatment .
B-Cell Acute Lymphoblastic Leukemia (B-ALL): CD20 upregulation post-induction therapy enables targeted immunotherapy integration .
Multiple Sclerosis: Ocrelizumab (anti-CD20) demonstrates superior efficacy over interferon β-1a, with manageable safety .
CD20 Loss: Gene splicing (e.g., alternative splicing of MS4A1) can reduce CD20 expression, diminishing therapeutic efficacy .
Plasma Cell Impact: CD20 antibodies spare plasma cells, preserving long-term humoral immunity .
CAR-T Therapy Limitations: CD20-negative relapses prompt dual-target CAR-T cells (e.g., CD19 + CD20) .
CD20 is a non-glycosylated phosphoprotein expressed on the surface of B cells. It plays a crucial role in B cell development and differentiation. The CD20 antigen is a target for monoclonal antibody therapies, particularly in the treatment of B cell malignancies such as non-Hodgkin lymphoma and chronic lymphocytic leukemia.
CD20, also known as MS4A1, is a membrane-spanning protein with four transmembrane domains. It is involved in the regulation of calcium influx across the plasma membrane, which is essential for B cell activation and proliferation. CD20 is expressed on the surface of all mature B cells but is absent on early B cell progenitors and plasma cells .
Monoclonal antibodies (mAbs) targeting CD20 have revolutionized the treatment of B cell malignancies. These antibodies bind specifically to the CD20 antigen on the surface of B cells, leading to their destruction through various mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct induction of apoptosis .
Recombinant monoclonal antibodies are produced using recombinant DNA technology, which allows for the generation of antibodies with high specificity and affinity. The development of recombinant anti-CD20 antibodies involves the insertion of the gene encoding the antibody into a host cell line, such as Chinese hamster ovary (CHO) cells, which then produce the antibody in large quantities .
The first anti-CD20 monoclonal antibody approved for clinical use was rituximab, a chimeric mouse/human antibody. Rituximab has been widely used in the treatment of various B cell malignancies and autoimmune diseases. Other anti-CD20 antibodies, such as ofatumumab and obinutuzumab, have been developed to improve efficacy and reduce immunogenicity .