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CD20 is a B-cell marker; rituximab against it was the first antibody approved for cancer, in 1997.
CD20 (MS4A1) is a B-cell tetraspanin that regulates calcium flux; it is not internalised, which favours effector-based antibodies and T-cell engagers over ADCs, and it is present on over 95% of DLBCL and, more dimly, over 90% of CLL. It is the target of rituximab, the first antibody approved for cancer in 1997, and of obinutuzumab. The CD20×CD3 bispecifics glofitamab, epcoritamab, mosunetuzumab, and odronextamab now offer off-the-shelf T-cell redirection in lymphoma without the manufacturing wait of CAR-T. Loss of CD20 expression is a recognised escape route after repeated anti-CD20 therapy, and the best sequencing of bispecifics versus CAR-T is still being worked out. The simple version is the B-cell marker that started antibody therapy for cancer and now anchors the newest T-cell engagers.
In plain words · CD20 is a B-cell marker; rituximab against it was the first antibody approved for cancer, in 1997.
Backbone ribbon from PDB 6Y97. RCSB PDB 6Y97. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
CD20 is a B-cell marker; rituximab against it was the first antibody approved for cancer, in 1997.
CD20 is a tetraspanin regulating B-cell calcium flux; it is not internalised, favouring effector-based antibodies over ADCs.
13 products aim at CD20: antibodies, bispecific antibodies, cell therapies and radioligands. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Lineage antigen shared with normal B-cells and lymphoid tissue cells: the label readouts filed under it score its expression (CD20 expression (CD20-positive)), and HPA finds the gene lineage enriched in that blood lineage at or above 25 nTPM, so medicines aimed at it clear the normal lineage too. HPA MS4A1: RNA tissue enriched (lymphoid tissue 631 nTPM); blood lineage lineage enriched (B-cells 630 nTPM); high antibody staining in 4 normal tissues; highest cancer staining lymphoma (11 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Leukaemia); Open Targets associates it with 6 specific cancer types at or above 0.5 (B-cell chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, non-Hodgkin lymphoma, acute lymphoblastic leukemia, B-cell non-Hodgkin lymphoma). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: CD20 expression (CD20-positive) label threshold; Human Protein Atlas MS4A1 tissue; Human Protein Atlas MS4A1 pathology; Open Targets ENSG00000156738 associations
First described 1988. Earliest sequence paper UniProt cites for the protein: Stamenkovic et al, J. Exp. Med, 1988, "Analysis of two cDNA clones encoding the B lymphocyte antigen CD20 (B1, Bp35), a type III integral membrane protein". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
CD20 is a tetraspanin regulating B-cell calcium flux; it is not internalised, favouring effector-based antibodies over ADCs.
RNA: tissue enriched (lymphoid tissue 631 nTPM), detected in many normal tissues. Blood: lineage enriched (B-cells 630 nTPM).
Medium: Bone marrow, Colon, Rectum, Skin.
HPA MS4A1 tissue · HPA MS4A1 pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Diffuse large B-cell lymphoma | >95% | Surface expression | Wikipedia | |
| Chronic lymphocytic leukaemia | >90% | Dim surface expression | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AZD5492 is an experimental T-cell engager from AstraZeneca in phase 2 trials, aimed at CD20.
Epcoritamab is an under-the-skin injection that pulls T cells onto lymphoma cells; it is approved for relapsed large B-cell and follicular lymphoma, and moving toward first line.
Glofitamab is a fixed-duration bispecific for large B-cell lymphoma, with OS benefit when combined with chemotherapy.
Zevalin is an antibody carrying a radioactive isotope that seeks out CD20 on lymphoma cells. It treats follicular lymphoma that has relapsed and is given as a one-off consolidation after chemotherapy.
JNJ-90014496 is an experimental CAR-T cell therapy from Janssen Research & Development in phase 2 trials for hodgkin lymphoma and diffuse large B-cell lymphoma, aimed at CD19 and CD20.
Mosunetuzumab is a fixed-duration CD20 bispecific approved for follicular lymphoma and studied with polatuzumab in large B-cell lymphoma.
Obinutuzumab is a glycoengineered CD20 antibody that recruits immune cells and kills B cells more directly than rituximab. Paired with venetoclax for a fixed 12 months in chronic lymphocytic leukaemia, it keeps over half of patients treatment-free six years later, and it is also used in follicular lymphoma; first-dose infusion reactions are common and managed by splitting the dose.
Odronextamab is Regeneron's CD20 bispecific, approved in Europe for lymphoma and in the US for follicular lymphoma after earlier FDA rejections over confirmatory-trial enrolment.
Ofatumumab (Arzerra) is a fully human anti-CD20 antibody for chronic lymphocytic leukaemia, used with chlorambucil in untreated patients or alone after other drugs have failed; the same molecule is sold as Kesimpta for multiple sclerosis.
Rituximab was the first antibody ever approved for cancer (1997). It made chemoimmunotherapy the CLL standard for a decade, and biosimilars keep it cheap and everywhere.
Rondecabtagene autoleucel is an experimental CAR-T cell therapy from Lyell Immunopharma in phase 3 trials for diffuse large B-cell lymphoma and hodgkin lymphoma, aimed at CD19 and CD20.
TQB2825 is an experimental bispecific antibody from Chia Tai Tianqing Pharmaceutical in phase 2 trials for diffuse large B-cell lymphoma, aimed at CD20 and CD3.
Zamtocabtagene autoleucel is an experimental CAR-T cell therapy from Miltenyi Biomedicine in phase 2 trials for diffuse large B-cell lymphoma, primary CNS lymphoma and mantle cell lymphoma, aimed at CD19 and CD20.
An option with a demonstrated survival benefit for transplant-ineligible relapsed diffuse large B-cell lymphoma, a group for whom very little has ever shown one. The fatal adverse event imbalance belongs in the conversation alongside the survival figure.
A new combination for relapsed or refractory follicular lymphoma that adds a CD19-directed antibody to the established lenalidomide and rituximab pairing, with the largest progression-free survival hazard ratio reported in the setting.
A second randomised confirmation that adding a Bruton tyrosine kinase inhibitor to first-line bendamustine-rituximab delays progression in older patients with mantle cell lymphoma, with a toxicity profile that did not improve as much as the drug's selectivity promised.
AMPLIFY delivered the first all-oral, fixed-duration doublet for front-line CLL and supported its approval, giving fit patients a way to avoid both chemotherapy and years of continuous BTK inhibitor. It does not settle whether a doublet or triplet is best, or how AV compares with venetoclax-obinutuzumab. Patients with TP53 aberration were excluded and still need different strategies.
The evidence behind the United States approval of brentuximab vedotin with lenalidomide and a rituximab product for relapsed or refractory diffuse large B-cell lymphoma after two or more lines in patients not eligible for an autologous transplant or CAR-T. It is also the first demonstration that a CD30-directed conjugate helps in a disease where CD30 expression is variable.
The authors' conclusion is that ibrutinib-rituximab should be considered a new standard-of-care option for first-line treatment of older patients with mantle-cell lymphoma. The subgroup split means it is clearly better than R-CHOP and roughly equivalent to bendamustine-rituximab.
An off-the-shelf alternative to CAR-T for repeatedly relapsed follicular lymphoma: no apheresis, no manufacturing wait, and a complete response rate in the same range, at the cost of continued treatment rather than a single infusion.
CD20 x CD3 bispecifics gave patients whose lymphoma has failed CAR-T, or who cannot access it, an effective off-the-shelf treatment that can be started within days. Epcoritamab and glofitamab are now standard third-line options and are moving into earlier lines and combinations. They do not yet replace CAR-T, whose remissions appear more durable.
Query for this target: (TITLE:"CD20" OR ABSTRACT:"CD20" OR TITLE:"MS4A1" OR ABSTRACT:"MS4A1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CD20, not a curated reading list.
Shares B cell, Complement in cancer, What it costs to aim at a lineage antigen, NK-cell recognition: missing self & stress ligands and the tag antibody-target.
Shares ELEVATE-TN, ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma, AMPLIFY, ROSEWOOD.
Shares ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma, ROSEWOOD, A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL, ARCHED.
Shares Study of Allo-QuadCAR01-T, an Allogeneic CAR-T Targeting CD19/CD20, in Patients With Relapsed or Refractory B-Cell Malignancies, Christopher R. Flowers, JNJ-90014496, Cellogen Therapeutics.
Shares T-cell/histiocyte-rich large B-cell lymphoma, Mediastinal grey zone lymphoma, Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma, ARCHED.
Shares TQB2825, Michael Dickinson, A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Adult Patients With B-cell Non-Hodgkin Lymphoma Who Have Been Previously Treat, Catherine Thieblemont.
Shares Barbara Eichhorst, John F. Seymour, Kirsten Fischer, Venetoclax + obinutuzumab (12 months).
Shares Hervé Tilly, Laurie H. Sehn, Gilles Salles, Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin in relapsed or refractory diffuse large B-cell lymphoma: results from the phase III, randomized POLARGO trial.