CD3G as a Radioligand Therapy Target
CD3G, CD3 gamma subunit of T-cell receptor complex, is a cell-surface protein (membrane receptor). In Human Protein Atlas immunohistochemistry, CD3G staining is highest in thyroid cancer (100% of samples positive), endometrial cancer (75% of samples positive) and neuroendocrine tumors (50% of samples positive). Published literature reports that CD3G internalizes after ligand binding, which helps retain a radionuclide inside tumor cells. Clinical status: Clinical-stage (up to phase 2, any modality).
Is CD3G a good radioligand therapy target?
Scored against the six criteria that decide whether a protein can become a radioligand therapy:
- ✅ Cell-surface accessibility: Localized to the cell surface, so a radioligand can reach it from circulation.
- ✅ Tumor expression: High IHC staining in thyroid cancer, 100% of samples positive.
- ✅ Internalization: Reported to internalize, which favors radionuclide retention.
- ✅ Clinical precedent: Clinical-stage (up to phase 2, any modality)
- ❔ Shedding: Not yet assessed.
- ❔ Normal-tissue dosimetry: Check kidney, liver, bone marrow and salivary expression in the Human Protein Atlas tissue atlas.
CD3G expression in cancer
Protein expression of CD3G across 20 cancer types from Human Protein Atlas immunohistochemistry. The score is a weighted staining intensity from 0 to 1; "% positive" is the share of patient samples with detectable staining.
| Cancer type | IHC score | Level | % positive |
|---|---|---|---|
| Thyroid Cancer | 0.78 | High | 100% |
| Endometrial Cancer | 0.31 | Medium | 75% |
| Neuroendocrine Tumors | 0.25 | Medium | 50% |
| Head and Neck Cancer | 0.22 | Medium | 33% |
| Colorectal Cancer | 0.21 | Medium | 46% |
| Prostate Cancer | 0.17 | Low | 40% |
| Pancreatic Cancer | 0.12 | Low | 27% |
| Gastric Cancer | 0.10 | Low | 20% |
| Cervical Cancer | 0.09 | Low | 18% |
| Ovarian Cancer | 0.06 | Low | 18% |
| Melanoma | 0.06 | Low | 18% |
| Lung Cancer | 0.06 | Low | 9% |
| Liver Cancer | 0.06 | Low | 9% |
| Kidney Cancer | 0.06 | Low | 8% |
| Glioma | 0.03 | Low | 8% |
Not detected by IHC in: skin cancer, lymphoma, breast cancer, bladder cancer, testicular cancer.
Is CD3G internalized?
Yes. TCR triggering induces an enhancement in the endocytic rate constant leading to TCR down-regulation.
Sources: PMID 14995914. AI-extracted from abstracts, so verify before citing.
CD3G clinical trials
Clinical-stage (up to phase 2, any modality). Nuclens hasn't indexed trials for CD3G yet. Search ClinicalTrials.gov for CD3G trials.
CD3G normal tissue expression
Normal-tissue expression in dose-limiting organs (kidney, liver, bone marrow, salivary glands) drives radioligand dosimetry risk. Nuclens is re-validating its normal-tissue values, so they are not shown here yet. See CD3G in the Human Protein Atlas tissue atlas, and read how normal-tissue expression predicts radioligand dosimetry risk.
CD3G gene essentiality (DepMap)
CRISPR knockout effect across 1226 cancer cell lines: 0.01 (not essential). Radioligands kill by radiation, not by blocking the target, so essentiality matters less than for inhibitors. A non-essential target can still be an excellent radioligand target.
Related thyroid cancer radioligand targets
c-MET (MET) · HER3 (ERBB3) · EPCAM · SSTR2 · EGFR · ITGAV · STEAP2 · FAP
See all radioligand therapy targets in thyroid cancer.
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Subcellular localization: UniProt via Open Targets (CC BY 4.0 / CC0). Tumor immunohistochemistry: Human Protein Atlas (CC BY-SA 4.0). Clinical trials: ClinicalTrials.gov (public domain). Gene essentiality: DepMap (CC BY 4.0). Internalization and shedding: AI-extracted from PubMed abstracts, so verify against the cited papers before relying on them. Nuclens is a first-pass triage layer, not a substitute for wet-lab validation or clinical dosimetry. Derived expression data on this page is shared under CC BY-SA 4.0.