CD3E CD3 epsilon subunit of T-cell receptor complex
ENSG00000198851 · protein coding · Open Targets profile
Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response (PubMed:15294938, PubMed:15546002, PubMed:2470098, PubMed:40592325, PubMed:8490660). When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z (PubMed:2470098, PubMed:40592325). All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain (PubMed:2470098, PubMed:40592325). Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098, PubMed:40592325). CD3E ITAM phosphorylation creates docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (By similarity). In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell development (By similarity). Also participates in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region (PubMed:10384095, PubMed:26507128). In addition to its role as a TCR coreceptor, it serves as a receptor for ITPRIPL1 (PubMed:38614099). Ligand recognition inhibits T-cell activation by promoting interaction with NCK1, which prevents CD3E-ZAP70 interaction and blocks the ERK- NFkB signaling cascade and calcium influx (PubMed:12110186, PubMed:38614099). {ECO:0000250|UniProtKB:P22646, ECO:0000269|PubMed:10384095, ECO:0000269|PubMed:12110186, ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:15546002, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:26507128, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:40592325, ECO:0000269|PubMed:8490660}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand, Med-Quality Pocket
- Antibody
- Approved Drug, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Database Ubiquitination, Half-life Data
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.46140000224113464 (upper bound 0.7007799744606018). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against CD3E (tarlatamab, talquetamab, epcoritamab, odronextamab, mosunetuzumab, muromonab-cd3, blinatumomab, teplizumab, glofitamab, teclistamab, elranatamab, otelixizumab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Elias JabbourM.D. Anderson Cancer Center · 8 of 8 trials Phase 2+Ph2NCT03263572 · Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemiabrief
- Dai ChiharaUT MD Anderson Cancer Center · 4 of 4 trials Phase 2+Ph2NCT07917832 · Smart 3: A Multi-Center Phase 2 Trial Of Golcadomide, Glofitamab And Polatuzumab Vedotin (G2P) For Patients With Newly Diagnosed Large B-Cell Lymphomabrief
- Mengyang DiFred Hutch/University of Washington Cancer Consortium · 3 of 3 trials Phase 2+
- Joseph M TuscanoCity of Hope Comprehensive Cancer Center LAO · 2 of 3 trials Phase 2+Ph1NCT06015880 · Testing the Combination of Anti-cancer Drugs Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphomabrief
- Anjali S AdvaniSWOG Network Cancer Center · 2 of 2 trials Phase 2+
- Jason WestinM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Marco LadettoDepartment of Translational Medicine of the Università degli Studi del Piemonte Orientale, Novara, Italy. AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy. · 2 of 2 trials Phase 2+
- Niels van de DonkAmsterdam UMC, Vrije Universiteit Amsterdam · 2 of 2 trials Phase 2+
- Noopur RajeMassachusetts General Hospital · 2 of 2 trials Phase 2+
- Pallawi TorkaMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Peng LiuFudan University · 2 of 2 trials Phase 2+
- Ryan LynchFred Hutch/University of Washington Cancer Consortium · 2 of 2 trials Phase 2+
- Salah-Eddin Al-BatranInstitut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · 2 of 2 trials Phase 2+
- Suning ChenThe First Affiliated Hospital of Soochow University Principal Investigator · 2 of 2 trials Phase 2+
- Swetha KambhampatiCity of Hope Medical Center · 2 of 2 trials Phase 2+
Registry trials of tarlatamab, talquetamab, epcoritamab, odronextamab, mosunetuzumab, muromonab-cd3, blinatumomab, teplizumab, glofitamab, teclistamab, elranatamab, otelixizumab updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 236 of 376 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 24 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
87 trials of drugs against CD3E were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of tarlatamab, talquetamab, epcoritamab, odronextamab, mosunetuzumab, muromonab-cd3, blinatumomab, teplizumab, glofitamab, teclistamab, elranatamab, otelixizumab, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 87.
- terminated · 2026-10-23 · Genmab · Epcoritamab“The study was terminated because sufficient data had been collected to meet the objectives of the development program. No new or unexpected safety findings were identified, and the decision to terminate was not related to participant safety.”
- suspended · 2026-10-08 · M.D. Anderson Cancer Center · Blinatumomab“PI requested”
- suspended · 2026-10-07 · City of Hope Medical Center · Talquetamab“pending amendment”
- terminated · 2026-09-18 · Grupo Espanol de Tumores Neuroendocrinos · Tarlatamab“AMGEN, due to a change in priorities within the Tarlatamab programme, has decided to withdraw its support for the study, which means the clinical trial will be terminated early.”
- terminated · 2026-08-17 · Regeneron Pharmaceuticals · matched by the registry's drug synonyms“Unfavorable benefit-risk assessment”
- terminated · 2026-05-06 · Pfizer · Glofitamab“Business/Administrative decision to pursue other programs/assets within the oncology portfolio. Not due to any detected safety signals or requests from regulatory authorities.”
- withdrawn · 2026-04-28 · National Cancer Institute (NCI) · Tarlatamab“Study drug supplier withdrew support; no participants were enrolled.”
- terminated · 2026-04-24 · Pfizer · Elranatamab + Nirogacestat, Elranatamab + lenalidomide + dexamethasone“A business decision was made by Pfizer to terminate the study and not proceed with the Phase 2 expansion of this study. The reason for study termination is not due to any safety concerns or requests from regulatory authorities.”
- withdrawn · 2026-04-07 · Memorial Sloan Kettering Cancer Center · Epcoritamab“Lack of accrual”
- terminated · 2026-03-06 · Imugene Limited · Blinatumomab“Portfolio prioritization”
- suspended · 2026-01-21 · City of Hope Medical Center · Epcoritamab“Pending Interim Analysis”
- suspended · 2025-10-23 · Mirror Biologics, Inc. · matched by the registry's drug synonyms“Sponsor unable to fund”
- withdrawn · 2025-09-17 · M.D. Anderson Cancer Center · Glofitamab“PI Request”
- withdrawn · 2025-08-15 · Janssen Research & Development, LLC · Talquetamab“Business Decision”
- terminated · 2025-07-29 · University of Washington · Teclistamab“Study terminated due to end of funding.”
- terminated · 2025-05-23 · Massachusetts General Hospital · Blinatumomab“Study closed early due to slow accrual”
- terminated · 2025-05-18 · Amgen · Blinatumomab“The decision to terminate is not based on safety or efficacy but due to slow enrollment impacting the ability to complete the study as planned.”
- terminated · 2025-05-13 · Michael Burke · Blinatumomab“poor accrual”
- withdrawn · 2025-03-03 · Jack Khouri, MD · Teclistamab(FDA-approved)“Funding unavailable”
- terminated · 2024-10-24 · Genmab · Epcoritamab“Due to strategic evaluation of GEN3009 within context of Genmab's portfolio, decision not based on any safety or regulatory concerns.”
- terminated · 2024-10-04 · Hoffmann-La Roche · Mosunetuzumab SC“Study was terminated due to Sponsor decision.”
- terminated · 2024-08-23 · Hoffmann-La Roche · Glofitamab“The study was terminated due to sponsor portfolio re-alignment.”
- terminated · 2024-08-01 · IGM Biosciences, Inc. · matched by the registry's drug synonyms“Company Decision”
- withdrawn · 2024-07-24 · Immunocore Ltd · matched by the registry's drug synonymsNo reason given
- withdrawn · 2024-03-12 · Ludwig-Maximilians - University of Munich · Blinatumomab in combination with donor lymphocyte infusion“Lack of potential study subjects due to a change of standard of care treatment outside of clinical trials.”
Paediatric incentives and obligations for CD3E's drugs
For tarlatamab, talquetamab, epcoritamab, odronextamab, mosunetuzumab, muromonab-cd3, blinatumomab, teplizumab, glofitamab, teclistamab, elranatamab, otelixizumab: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · CD3E is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000181993 (mosunetuzumab, Treatment of mature B-cell neoplasms): PM: decision on the application for modification of an agreed PIP, 8 Nov 2024; EMA/PE/0000243095 (teplizumab, Treatment of type I diabetes mellitus): PM: decision on the application for modification of an agreed PIP, 16 Jan 2025; EMA/PE/0000221213 (blinatumomab, Treatment of B-lymphoblastic leukaemia/lymphoma): PM: decision on the application for modification of an agreed PIP, 3 Jan 2025; EMEA-000524-PIP02-24 (teplizumab, Prevention of stage 3 type 1 diabetes mellitus): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 25 Oct 2024; +4 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/21/2486 withdrawn 20 Aug 2021: Treatment of multiple myeloma; EU/3/23/2876 positive 12 Jan 2024: Treatment of small cell lung cancer; EU/3/21/2497 withdrawn 15 Oct 2021: Treatment of diffuse large B-cell lymphoma; EU/3/22/2656 withdrawn 18 Jul 2022: Treatment of diffuse large B-cell lymphoma; +9 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Talvey: authorised since 21 Aug 2023, conditional; Tecvayli: authorised since 23 Aug 2022; Columvi: authorised since 7 Jul 2023; Lunsumio: authorised since 3 Jun 2022, orphan medicine, conditional; +6 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: yes · Blinatumomab [Blincyto], 14 Jun 2024: Treatment of CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL) in the consolidation phase of multiphase chemotherapy in adult and pediatric patients one month and older; Blinatumomab [Blincyto], 29 Mar 2018: Treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adult and pediatric patients one month and older; Blinatumomab [Blincyto], 11 Jul 2017: Treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and olderRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 128 interventional studies of tarlatamab, talquetamab, epcoritamab, odronextamab, mosunetuzumab, muromonab-cd3, blinatumomab, teplizumab, glofitamab, teclistamab, elranatamab, otelixizumab include patients under 18; 70 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 22 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.