# CD20

Source: https://onco.cc/targets/cd20/  
OnCo record `cd20` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

CD20 is a B-cell marker; rituximab against it was the first antibody approved for cancer, in 1997.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: antibody-target
- Symbol: MS4A1
- Class: surface-antigen
- Biology: CD20 is a tetraspanin regulating B-cell calcium flux; it is not internalised, favouring effector-based antibodies over ADCs.
- Where found: DLBCL; Follicular lymphoma; CLL; Mantle cell lymphoma

## Notes

- Lymphoma: Almost every mature B-cell lymphoma: diffuse large B-cell, follicular, marginal zone, mantle cell, Burkitt, and the B cells of nodular lymphocyte-predominant Hodgkin lymphoma. Also on healthy cells: Every normal B cell from the late pre-B stage to the memory B cell. The Human Protein Atlas reads MS4A1 as tissue enriched in lymphoid tissue (631 nTPM) and lineage enriched in B cells (630 nTPM), which is the strongest B-cell signal of any lymphoma surface target. What the medicine does: CD20 is a tetraspanin that is not internalised when an antibody binds it, so the antibody has to kill from the outside: complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and phagocytosis. That is why CD20 carries naked antibodies (rituximab, obinutuzumab, ofatumumab) and T-cell engagers (glofitamab, mosunetuzumab, epcoritamab, odronextamab) but no antibody-drug conjugate: there is no route in for a payload. How tumours lose it: CD20-negative transformation after rituximab is real and under-measured because most relapses are not rebiopsied. In a single-centre series of 124 patients treated with rituximab-containing chemotherapy, 36 relapsed or progressed, 19 were rebiopsied and 5 of those 19 (26.3%) had become CD20 protein-negative; CD20 messenger RNA was lower in the negative cells than in the positive cells from the same patient, so this is transcriptional down-regulation rather than deletion (Hiraga 2009). Trogocytosis, in which macrophages shave antibody-CD20 complexes off the cell surface, lowers the antigen without changing the gene at all. What that costs the patient: B-cell aplasia for six to twelve months after the last dose, low immunoglobulin levels that can persist for years, and a measurable rise in bacterial and viral infection. Two consequences are specific and avoidable: hepatitis B reactivation, which is why surface antigen and core antibody are checked before the first dose, and a blunted response to vaccination for several months after treatment.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/CD20
- Wikipedia: https://en.wikipedia.org/wiki/CD20
- Hiraga et al., Blood 2009: CD20-negative transformation after rituximab-containing chemotherapy (19 rebiopsied patients): https://doi.org/10.1182/blood-2008-08-175208

## Connected records

- biomarkers: [CD20 expression (CD20-positive)](https://onco.cc/biomarkers/cd20-expression/)
- cancers: [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)](https://onco.cc/cancers/malt-lymphoma/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Hairy cell leukaemia](https://onco.cc/cancers/hairy-cell-leukemia/), [HIV-associated (AIDS-related) lymphomas](https://onco.cc/cancers/hiv-associated-lymphoma/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Mediastinal grey zone lymphoma](https://onco.cc/cancers/mediastinal-grey-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Post-transplant lymphoproliferative disorder (PTLD)](https://onco.cc/cancers/post-transplant-lymphoproliferative-disorder/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/), [Primary mediastinal (thymic) large B-cell lymphoma](https://onco.cc/cancers/primary-mediastinal-b-cell-lymphoma/), [Relapsed or refractory chronic lymphocytic leukaemia](https://onco.cc/cancers/cll-relapsed/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [T-cell/histiocyte-rich large B-cell lymphoma](https://onco.cc/cancers/t-cell-histiocyte-rich-large-b-cell-lymphoma/), [Waldenström macroglobulinaemia](https://onco.cc/cancers/waldenstrom/)
- drugs: [AZD5492](https://onco.cc/drugs/azd5492/), [Epcoritamab](https://onco.cc/drugs/epcoritamab/), [Glofitamab](https://onco.cc/drugs/glofitamab/), [Ibritumomab tiuxetan](https://onco.cc/drugs/ibritumomab-tiuxetan/), [JNJ-90014496](https://onco.cc/drugs/jnj-90014496/), [Mosunetuzumab](https://onco.cc/drugs/mosunetuzumab/), [Obinutuzumab](https://onco.cc/drugs/obinutuzumab/), [Odronextamab](https://onco.cc/drugs/odronextamab/), [Ofatumumab](https://onco.cc/drugs/ofatumumab/), [Rituximab](https://onco.cc/drugs/rituximab/), [Rondecabtagene autoleucel](https://onco.cc/drugs/rondecabtagene-autoleucel/), [TQB2825](https://onco.cc/drugs/tqb2825/), [Zamtocabtagene autoleucel](https://onco.cc/drugs/zamtocabtagene-autoleucel/)
- companies: [Cellogen Therapeutics](https://onco.cc/companies/cellogen/), [Dr. Reddy's Laboratories](https://onco.cc/companies/dr-reddys/), [Hetero Drugs](https://onco.cc/companies/hetero/), [Interius BioTherapeutics](https://onco.cc/companies/interius/), [LEAH Labs](https://onco.cc/companies/leah-labs/), [Lyell Immunopharma](https://onco.cc/companies/lyell-immunopharma/), [Poseida Therapeutics](https://onco.cc/companies/poseida-therapeutics/), [TG Therapeutics](https://onco.cc/companies/tg-therapeutics/)
- trials: [A Phase 3 Study to Assess Efficacy and Safety of Tafasitamab Plus Lenalidomide and Rituximab Compared to Placebo Plus Lenalidomide and Rituximab in Pa](https://onco.cc/trials/nct04680052/), [A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL](https://onco.cc/trials/nct02972840/), [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](https://onco.cc/trials/nct03888105/), [AMPLIFY](https://onco.cc/trials/amplify/), [ARCHED](https://onco.cc/trials/arched/), [Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL](https://onco.cc/trials/nct04404283/), [CLL13 / GAIA](https://onco.cc/trials/cll13-gaia/), [CLL14](https://onco.cc/trials/cll14/), [ELEVATE-TN](https://onco.cc/trials/elevate-tn/), [ENRICH](https://onco.cc/trials/enrich/), [FORTplus](https://onco.cc/trials/fortplus/), [GOYA](https://onco.cc/trials/goya/), [IELSG-19](https://onco.cc/trials/ielsg-19/), [Inter-B-NHL Ritux 2010](https://onco.cc/trials/inter-b-nhl-ritux-2010/), [LyMa](https://onco.cc/trials/lyma/), [Mosunetuzumab against rituximab in low tumour burden follicular lymphoma](https://onco.cc/trials/mosun-lbt-fl/), [Mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma](https://onco.cc/trials/mosun-len-mzl/), [POLAR BEAR](https://onco.cc/trials/polar-bear/), [POLARGO](https://onco.cc/trials/polargo/), [PRIMA](https://onco.cc/trials/prima-follicular/), [PRIMA-CNS](https://onco.cc/trials/prima-cns/), [ROSEWOOD](https://onco.cc/trials/rosewood/), [SHINE](https://onco.cc/trials/shine/), [Study of Allo-QuadCAR01-T, an Allogeneic CAR-T Targeting CD19/CD20, in Patients With Relapsed or Refractory B-Cell Malignancies](https://onco.cc/trials/nct07284433/)
- pairings: [Venetoclax + obinutuzumab (12 months)](https://onco.cc/pairings/venetoclax-plus-obinutuzumab/)
- terms: [Antigen escape: how a lymphoma loses the thing the drug was aimed at](https://onco.cc/terms/lymphoma-bio-antigen-escape/), [B cell](https://onco.cc/terms/b-cell/), [B-cell, T-cell and NK-cell lymphoma](https://onco.cc/terms/lymphoma-b-versus-t-cell/), [Lymphoma (tissue type)](https://onco.cc/terms/lymphoma-type/), [What it costs to aim at a lineage antigen](https://onco.cc/terms/lymphoma-bio-lineage-antigen-cost/)
- key papers: [Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma](https://onco.cc/key-papers/paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025/), [AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients](https://onco.cc/key-papers/paper-amplify-acalabrutinib-venetoclax-nejm-2025/), [Brentuximab vedotin combination for relapsed diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-echelon-3-brentuximab-lenalidomide-rituximab-dlbcl-jco-2025/), [CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients](https://onco.cc/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/), [ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL](https://onco.cc/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/), [EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-T](https://onco.cc/key-papers/paper-epcore-nhl-1-epcoritamab-jco-2023/), [Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy](https://onco.cc/key-papers/paper-ielsg-19-chlorambucil-rituximab-malt-jco-2017/), [Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial](https://onco.cc/key-papers/paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025/), [Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma](https://onco.cc/key-papers/paper-shine-ibrutinib-bendamustine-rituximab-mantle-cell-nejm-2022/), [MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL](https://onco.cc/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/), [Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-goya-obinutuzumab-vs-rituximab-chop-dlbcl-jco-2017/), [POLARIX: swapping vincristine for the antibody-drug conjugate polatuzumab vedotin in first-line treatment of diffuse large B-cell lymphoma](https://onco.cc/key-papers/paper-polarix-polatuzumab-rchp-nejm-2022/), [Polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin in relapsed or refractory diffuse large B-cell lymphoma: results from the phase III, randomized POLARGO trial](https://onco.cc/key-papers/paper-polargo-polatuzumab-r-gemox-dlbcl-jco-2026/), [Randomized phase III trial of ibrutinib and R-CHOP in non-germinal centre B-cell diffuse large B-cell lymphoma (PHOENIX)](https://onco.cc/key-papers/paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019/), [Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma](https://onco.cc/key-papers/paper-lyma-rituximab-maintenance-after-transplant-mantle-cell-nejm-2017/), [Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial](https://onco.cc/key-papers/paper-prima-rituximab-maintenance-follicular-lancet-2011/), [ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma](https://onco.cc/key-papers/paper-rosewood-zanubrutinib-obinutuzumab-follicular-jco-2023/), [Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma](https://onco.cc/key-papers/paper-elm-2-odronextamab-follicular-ann-oncol-2024/), [Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study](https://onco.cc/key-papers/paper-prima-final-rituximab-maintenance-follicular-jco-2019/), [Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial](https://onco.cc/key-papers/paper-inmind-tafasitamab-lenalidomide-rituximab-follicular-lancet-2026/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)
- ideas: [An abbreviated approval path for follow-on antibodies within a validated class](https://onco.cc/ideas/idea-fund-abbreviated-pathway-me-too-biologics/), [Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas](https://onco.cc/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/), [Plan the second CAR-T target before the first one is lost](https://onco.cc/ideas/idea-bio1-adaptive-car-antigen-switch/)
- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- people: [Barbara Eichhorst](https://onco.cc/people/barbara-eichhorst/), [Catherine Thieblemont](https://onco.cc/people/catherine-thieblemont/), [Christopher R. Flowers](https://onco.cc/people/christopher-flowers/), [Gilles Salles](https://onco.cc/people/gilles-salles/), [Hervé Tilly](https://onco.cc/people/herve-tilly/), [John F. Seymour](https://onco.cc/people/john-seymour/), [Kirsten Fischer](https://onco.cc/people/kirsten-fischer/), [Laurie H. Sehn](https://onco.cc/people/laurie-sehn/), [Martin Dreyling](https://onco.cc/people/martin-dreyling/), [Michael Dickinson](https://onco.cc/people/michael-dickinson/), [Michael Hallek](https://onco.cc/people/michael-hallek/), [Ronald Levy](https://onco.cc/people/ronald-levy/), [Wyndham H. Wilson](https://onco.cc/people/wyndham-wilson/)
- institutions: [IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola](https://onco.cc/institutions/sant-orsola-bologna/), [University Hospital Southampton / Centre for Cancer Immunology](https://onco.cc/institutions/southampton-cancer/)
- pathways: [Complement in cancer](https://onco.cc/pathways/complement-in-cancer/), [NK-cell recognition: missing self & stress ligands](https://onco.cc/pathways/nk-cell-recognition/)

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