# CD3

Source: https://onco.cc/targets/cd3/  
OnCo record `cd3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: t-cell-engager-target
- Symbol: CD3E
- Class: surface-antigen
- Biology: Invariant TCR co-receptor; engagement triggers activation and cytokine release independent of MHC.
- Where found: All T cells (effector arm, not a tumour target)

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/CD3_(immunology)
- Wikipedia: https://en.wikipedia.org/wiki/CD3_(immunology)
- Kuppers, Nat Rev Cancer 2009: the biology of Hodgkin's lymphoma: https://doi.org/10.1038/nrc2542

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Relapsed and refractory acute lymphoblastic leukaemia in children](https://onco.cc/cancers/all-paediatric-relapsed/), [Uveal melanoma](https://onco.cc/cancers/uveal-melanoma/)
- drugs: [ASP2138](https://onco.cc/drugs/asp2138/), [AZD0486](https://onco.cc/drugs/azd0486/), [AZD5863](https://onco.cc/drugs/azd5863/), [AZD6621](https://onco.cc/drugs/azd6621/), [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Brenetafusp](https://onco.cc/drugs/brenetafusp/), [CART84](https://onco.cc/drugs/cart84/), [Catumaxomab](https://onco.cc/drugs/catumaxomab/), [Elranatamab](https://onco.cc/drugs/elranatamab/), [Epcoritamab](https://onco.cc/drugs/epcoritamab/), [Glofitamab](https://onco.cc/drugs/glofitamab/), [Linvoseltamab](https://onco.cc/drugs/linvoseltamab/), [M701](https://onco.cc/drugs/m701/), [Mosunetuzumab](https://onco.cc/drugs/mosunetuzumab/), [Obrixtamig](https://onco.cc/drugs/obrixtamig/), [Odronextamab](https://onco.cc/drugs/odronextamab/), [Pasritamig](https://onco.cc/drugs/pasritamig/), [Talquetamab](https://onco.cc/drugs/talquetamab/), [Tarlatamab](https://onco.cc/drugs/tarlatamab/), [Tebentafusp](https://onco.cc/drugs/tebentafusp/), [Teclistamab](https://onco.cc/drugs/teclistamab/), [TQB2825](https://onco.cc/drugs/tqb2825/), [Ubamatamab](https://onco.cc/drugs/ubamatamab/), [Xaluritamig](https://onco.cc/drugs/xaluritamig/)
- companies: [Asher Biotherapeutics](https://onco.cc/companies/asher-bio/), [Cullinan Therapeutics](https://onco.cc/companies/cullinan-therapeutics/), [CytomX Therapeutics](https://onco.cc/companies/cytomx-therapeutics/), [Harpoon Therapeutics](https://onco.cc/companies/harpoon-therapeutics/), [Janux Therapeutics](https://onco.cc/companies/janux-therapeutics/), [Xencor](https://onco.cc/companies/xencor/)
- trials: [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/), [COG AALL1731](https://onco.cc/trials/aall1731/), [ECOG-ACRIN E1910](https://onco.cc/trials/e1910/), [IMCgp100-202](https://onco.cc/trials/imcgp100-202/), [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/), [PRISM-MEL-301](https://onco.cc/trials/prism-mel-301/), [TOWER](https://onco.cc/trials/tower/)
- terms: [T cell](https://onco.cc/terms/t-cell/), [What it costs to aim at a lineage antigen](https://onco.cc/terms/lymphoma-bio-lineage-antigen-cost/)
- key papers: [Children's Oncology Group AALL1731: blinatumomab added to chemotherapy for children with standard-risk B-cell ALL](https://onco.cc/key-papers/paper-aall1731-blinatumomab-children-nejm-2025/), [DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer](https://onco.cc/key-papers/paper-dellphi-301-nejm-2023/), [ECOG-ACRIN E1910: adding blinatumomab to chemotherapy for adults with B-cell ALL already in MRD-negative remission](https://onco.cc/key-papers/paper-e1910-blinatumomab-mrd-negative-all-nejm-2024/), [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/), [MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response](https://onco.cc/key-papers/paper-magnetismm-3-elranatamab-natmed-2023/), [MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma](https://onco.cc/key-papers/paper-majestec-1-teclistamab-nejm-2022/), [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/)
- 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: [Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas](https://onco.cc/ideas/lymphoma-ev-fixed-duration-chemotherapy-free-first-line/)
- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- pathways: [Antigen presentation & immune editing](https://onco.cc/pathways/antigen-presentation-immunoediting/), [Extrinsic apoptosis (death receptors)](https://onco.cc/pathways/extrinsic-apoptosis-death-receptors/), [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [The cancer-immunity cycle](https://onco.cc/pathways/cancer-immunity-cycle/)
- people: [Ajai Chari](https://onco.cc/people/ajai-chari/), [Catherine Thieblemont](https://onco.cc/people/catherine-thieblemont/), [Elias Jabbour](https://onco.cc/people/elias-jabbour/), [Mark R. Litzow](https://onco.cc/people/mark-litzow/), [Michael Dickinson](https://onco.cc/people/michael-dickinson/), [Paul Nathan](https://onco.cc/people/paul-nathan/), [Philippe Moreau](https://onco.cc/people/philippe-moreau/), [Sumit Gupta](https://onco.cc/people/sumit-gupta/)
- targets: [HLA-A](https://onco.cc/targets/hla-a/)

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JSON: https://onco.cc/api/v1/entities/cd3.json