{"entity":{"id":"cd3","kind":"target","name":"CD3","aka":[],"tldr":"CD3 is the switch on every T cell. Bispecific drugs grab it with one arm and the tumour with the other, forcing the T cell to attack.","summary":"CD3 (gene CD3E) is the invariant signalling component of the T-cell receptor complex, and engaging it triggers T-cell activation and cytokine release independent of MHC presentation. It is found on all T cells and is therefore an effector handle rather than a tumour target. Every T-cell engager, including blinatumomab, teclistamab, tarlatamab, glofitamab and tebentafusp, uses an anti-CD3 arm to recruit any passing T cell to a tumour antigen bound by the other arm. Affinity tuning of the CD3 arm is the main lever on cytokine release syndrome, and step-up dosing is the standard clinical countermeasure. How much CD3 affinity, valency and format can be optimised to separate potency from toxicity is still being worked out. The plain version: bispecifics grab CD3 with one arm and the tumour with the other, forcing the T cell to attack.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD3_(immunology)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD3_(immunology)"},{"label":"Kuppers, Nat Rev Cancer 2009: the biology of Hodgkin's lymphoma","url":"https://doi.org/10.1038/nrc2542"}],"tags":["t-cell-engager-target"],"related":[],"cancers":["non-hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["catumaxomab","asp2138","azd0486","tqb2825","azd6621","cart84","azd5863"],"companies":["asher-bio","cullinan-therapeutics","cytomx-therapeutics","harpoon-therapeutics","janux-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not applicable: CD3 is the T-cell effector arm of bispecific engagers, not a tumour antigen, so no expression rate by cancer is recorded. Surface CD3 is present on most mature T-cell lymphomas, but that is not what the drugs select for.","Lymphoma: Every T cell in the body. In T-cell lymphoma the tumour carries it too, which is the central difficulty of treating T-cell disease with T cells. Also on healthy cells: All of them. CD3 is the one target in lymphoma that is not on the tumour at all in B-cell disease: it is the arm the bispecific antibody grips so that the other arm can hold the tumour. What the medicine does: A CD3-engaging bispecific antibody forces an immunological synapse between a T cell and a tumour cell without needing the T cell to recognise anything, so it bypasses the loss of antigen presentation that defeats a checkpoint inhibitor. Glofitamab, mosunetuzumab, epcoritamab and odronextamab all hold CD20 with the other arm; glofitamab holds two CD20 molecules to one CD3. How tumours lose it: The tumour does not lose CD3. What limits the class is the T cell: exhausted or scarce T cells after several lines of treatment, and the same CD20 loss that defeats rituximab. What that costs the patient: Cytokine release syndrome and neurotoxicity, which is why these drugs are given with a step-up dosing schedule over the first cycle, and why the first doses are given where a patient can be watched. The toxicity is the mechanism working, not a side reaction."],"symbol":"CD3E","role":[],"sources":[],"specificity":"immune-microenvironment","distribution":"many-types","specificityNote":"Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA CD3E: RNA tissue enriched (lymphoid tissue 596 nTPM); blood lineage group enriched (NK-cells 203 nTPM, T-cells 503 nTPM); high antibody staining in 3 normal tissues. Distribution: no corpus cancer carries a prevalence row, threshold or catalogue link for it; Open Targets associates it with 5 specific cancer types at or above 0.5 (plasma cell myeloma, diffuse large B-cell lymphoma, acute lymphoblastic leukemia, follicular lymphoma, small cell lung carcinoma). (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas CD3E tissue","url":"https://www.proteinatlas.org/ENSG00000198851-CD3E/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt P07766","url":"https://www.uniprot.org/uniprotkb/P07766/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000198851 associations","url":"https://platform.opentargets.org/target/ENSG00000198851/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:1674","ensembl":"ENSG00000198851","uniprot":"P07766","entrez":"916","firstDescribed":1986,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Gold D.P. et al, Nature, 1986, \"Isolation of cDNA clones encoding the 20K non-glycosylated polypeptide chain of the human T-cell receptor/T3 complex\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3012357/","biology":"Invariant TCR co-receptor; engagement triggers activation and cytokine release independent of MHC.","whereFound":["All T cells (effector arm, not a tumour target)"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"metastatic-cancer","pct":"immune","measure":"Immune-cell target (CD3 on every T cell, the arm that T-cell engagers pull on): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers."}]},"route":"/targets/cd3/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"all-paediatric-relapsed","kind":"cancer","name":"Relapsed and refractory acute lymphoblastic leukaemia in children","route":"/cancers/all-paediatric-relapsed/"},{"id":"uveal-melanoma","kind":"cancer","name":"Uveal melanoma","route":"/cancers/uveal-melanoma/"}],"drug":[{"id":"asp2138","kind":"drug","name":"ASP2138","route":"/drugs/asp2138/"},{"id":"azd0486","kind":"drug","name":"AZD0486","route":"/drugs/azd0486/"},{"id":"azd5863","kind":"drug","name":"AZD5863","route":"/drugs/azd5863/"},{"id":"azd6621","kind":"drug","name":"AZD6621","route":"/drugs/azd6621/"},{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/"},{"id":"brenetafusp","kind":"drug","name":"Brenetafusp","route":"/drugs/brenetafusp/"},{"id":"cart84","kind":"drug","name":"CART84","route":"/drugs/cart84/"},{"id":"catumaxomab","kind":"drug","name":"Catumaxomab","route":"/drugs/catumaxomab/"},{"id":"elranatamab","kind":"drug","name":"Elranatamab","route":"/drugs/elranatamab/"},{"id":"epcoritamab","kind":"drug","name":"Epcoritamab","route":"/drugs/epcoritamab/"},{"id":"glofitamab","kind":"drug","name":"Glofitamab","route":"/drugs/glofitamab/"},{"id":"linvoseltamab","kind":"drug","name":"Linvoseltamab","route":"/drugs/linvoseltamab/"},{"id":"m701","kind":"drug","name":"M701","route":"/drugs/m701/"},{"id":"mosunetuzumab","kind":"drug","name":"Mosunetuzumab","route":"/drugs/mosunetuzumab/"},{"id":"obrixtamig","kind":"drug","name":"Obrixtamig","route":"/drugs/obrixtamig/"},{"id":"odronextamab","kind":"drug","name":"Odronextamab","route":"/drugs/odronextamab/"},{"id":"pasritamig","kind":"drug","name":"Pasritamig","route":"/drugs/pasritamig/"},{"id":"talquetamab","kind":"drug","name":"Talquetamab","route":"/drugs/talquetamab/"},{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","route":"/drugs/tarlatamab/"},{"id":"tebentafusp","kind":"drug","name":"Tebentafusp","route":"/drugs/tebentafusp/"},{"id":"teclistamab","kind":"drug","name":"Teclistamab","route":"/drugs/teclistamab/"},{"id":"tqb2825","kind":"drug","name":"TQB2825","route":"/drugs/tqb2825/"},{"id":"ubamatamab","kind":"drug","name":"Ubamatamab","route":"/drugs/ubamatamab/"},{"id":"xaluritamig","kind":"drug","name":"Xaluritamig","route":"/drugs/xaluritamig/"}],"company":[{"id":"asher-bio","kind":"company","name":"Asher Biotherapeutics","route":"/companies/asher-bio/"},{"id":"cullinan-therapeutics","kind":"company","name":"Cullinan Therapeutics","route":"/companies/cullinan-therapeutics/"},{"id":"cytomx-therapeutics","kind":"company","name":"CytomX Therapeutics","route":"/companies/cytomx-therapeutics/"},{"id":"harpoon-therapeutics","kind":"company","name":"Harpoon Therapeutics","route":"/companies/harpoon-therapeutics/"},{"id":"janux-therapeutics","kind":"company","name":"Janux Therapeutics","route":"/companies/janux-therapeutics/"},{"id":"xencor","kind":"company","name":"Xencor","route":"/companies/xencor/"}],"trial":[{"id":"nct03888105","kind":"trial","name":"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","route":"/trials/nct03888105/"},{"id":"aall1731","kind":"trial","name":"COG AALL1731","route":"/trials/aall1731/"},{"id":"e1910","kind":"trial","name":"ECOG-ACRIN E1910","route":"/trials/e1910/"},{"id":"imcgp100-202","kind":"trial","name":"IMCgp100-202","route":"/trials/imcgp100-202/"},{"id":"mosun-lbt-fl","kind":"trial","name":"Mosunetuzumab against rituximab in low tumour burden follicular lymphoma","route":"/trials/mosun-lbt-fl/"},{"id":"mosun-len-mzl","kind":"trial","name":"Mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma","route":"/trials/mosun-len-mzl/"},{"id":"prism-mel-301","kind":"trial","name":"PRISM-MEL-301","route":"/trials/prism-mel-301/"},{"id":"tower","kind":"trial","name":"TOWER","route":"/trials/tower/"}],"term":[{"id":"t-cell","kind":"term","name":"T cell","route":"/terms/t-cell/"},{"id":"lymphoma-bio-lineage-antigen-cost","kind":"term","name":"What it costs to aim at a lineage antigen","route":"/terms/lymphoma-bio-lineage-antigen-cost/"}],"paper":[{"id":"paper-aall1731-blinatumomab-children-nejm-2025","kind":"paper","name":"Children's Oncology Group AALL1731: blinatumomab added to chemotherapy for children with standard-risk B-cell ALL","route":"/key-papers/paper-aall1731-blinatumomab-children-nejm-2025/"},{"id":"paper-dellphi-301-nejm-2023","kind":"paper","name":"DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer","route":"/key-papers/paper-dellphi-301-nejm-2023/"},{"id":"paper-e1910-blinatumomab-mrd-negative-all-nejm-2024","kind":"paper","name":"ECOG-ACRIN E1910: adding blinatumomab to chemotherapy for adults with B-cell ALL already in MRD-negative remission","route":"/key-papers/paper-e1910-blinatumomab-mrd-negative-all-nejm-2024/"},{"id":"paper-epcore-nhl-1-epcoritamab-jco-2023","kind":"paper","name":"EPCORE NHL-1: epcoritamab, a subcutaneous CD20 x CD3 bispecific, in relapsed large B-cell lymphoma including after CAR-T","route":"/key-papers/paper-epcore-nhl-1-epcoritamab-jco-2023/"},{"id":"paper-magnetismm-3-elranatamab-natmed-2023","kind":"paper","name":"MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response","route":"/key-papers/paper-magnetismm-3-elranatamab-natmed-2023/"},{"id":"paper-majestec-1-teclistamab-nejm-2022","kind":"paper","name":"MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma","route":"/key-papers/paper-majestec-1-teclistamab-nejm-2022/"},{"id":"paper-elm-2-odronextamab-follicular-ann-oncol-2024","kind":"paper","name":"Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma","route":"/key-papers/paper-elm-2-odronextamab-follicular-ann-oncol-2024/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/lymphoma-roadmap/"}],"idea":[{"id":"lymphoma-ev-fixed-duration-chemotherapy-free-first-line","kind":"idea","name":"Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas","route":"/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"},{"id":"extrinsic-apoptosis-death-receptors","kind":"pathway","name":"Extrinsic apoptosis (death receptors)","route":"/pathways/extrinsic-apoptosis-death-receptors/"},{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"cancer-immunity-cycle","kind":"pathway","name":"The cancer-immunity cycle","route":"/pathways/cancer-immunity-cycle/"}],"person":[{"id":"ajai-chari","kind":"person","name":"Ajai Chari","route":"/people/ajai-chari/"},{"id":"catherine-thieblemont","kind":"person","name":"Catherine Thieblemont","route":"/people/catherine-thieblemont/"},{"id":"elias-jabbour","kind":"person","name":"Elias Jabbour","route":"/people/elias-jabbour/"},{"id":"mark-litzow","kind":"person","name":"Mark R. Litzow","route":"/people/mark-litzow/"},{"id":"michael-dickinson","kind":"person","name":"Michael Dickinson","route":"/people/michael-dickinson/"},{"id":"paul-nathan","kind":"person","name":"Paul Nathan","route":"/people/paul-nathan/"},{"id":"philippe-moreau","kind":"person","name":"Philippe Moreau","route":"/people/philippe-moreau/"},{"id":"sumit-gupta","kind":"person","name":"Sumit Gupta","route":"/people/sumit-gupta/"}],"target":[{"id":"hla-a","kind":"target","name":"HLA-A","route":"/targets/hla-a/"}]}}