# 5T4 (trophoblast glycoprotein)

Source: https://nuclide.cc/targets/tpbg-5t4/  
Nuclide record `tpbg-5t4` (Target). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

A protein the placenta makes during pregnancy that many cancers switch back on while most healthy adult tissue does not. Antibody-drug conjugates against it have been tested in patients, and since 2024 the first radiolabelled versions have reached people in China.

## Summary

5T4, encoded by TPBG (HGNC:12004), is a 72 kD heavily N-glycosylated membrane protein with leucine-rich repeats, first found by searching for surface molecules shared between human trophoblast and cancer cells. It is expressed by many different cancers but rarely in normal adult tissue, and its expression is linked to epithelial-mesenchymal transition, CXCL12/CXCR4 chemotaxis and a tumour-initiating phenotype (Stern and Harrop, Cancer Immunol Immunother 2017).

The target was validated clinically as an antibody-drug conjugate first. Pfizer's PF-06263507, an anti-5T4 IgG1 carrying monomethylauristatin-F, was given to 26 patients in a first-in-human trial (NCT01891669): the maximum tolerated dose was 4.34 mg/kg, ocular toxicity caused the dose-limiting events, and no objective responses were seen in patients who were not selected for 5T4 expression. In mesothelioma, 5T4 was expressed in 10 of 12 cell lines and most biopsies, and antibodies and ADCs against it internalise into lysosomes.

Radiopharmaceutical work is recent and largely Chinese. A humanised single-domain antibody, [68Ga]Ga-NOTA-H006, went from camel immunisation to a pilot clinical study at Huashan Hospital, Fudan University, registered as NCT06162988, and mapped 5T4-positive lesions in patients with a mean effective dose of 0.034 mSv/MBq (EJNMMI 2025). An [18F]AlF-RESCA-H006 version was built for pancreatic adenocarcinoma, and a full-antibody theranostic pair, [89Zr]Zr-DFO-HB5 for imaging with [177Lu]Lu- and [161Tb]Tb-DOTA-HB5 for therapy, slowed tumour growth in two colorectal cancer xenograft models (J Med Chem 2026). A 2026 systematic review lists 5T4 with CEACAM5, TROP2, GPC3 and ROR1 as oncofetal surface antigens in advanced prostate cancer, including neuroendocrine and castration-resistant disease.

The open question is patient selection: the only ADC trial enrolled unselected patients and saw no responses, which is the gap a 5T4 imaging agent could close.

## Fields

- Kind: Target
- Last checked: 2026-09-24
- Also known as: 5T4; TPBG; 5T4 oncofetal antigen; WAIF1
- Tags: oncofetal antigen; antibody target; ADC-validated; China
- Symbol: TPBG
- Class: surface-antigen
- Biology: A heavily glycosylated leucine-rich-repeat membrane protein shared by trophoblast and cancer cells. It favours non-canonical over canonical Wnt signalling, potentiates CXCL12/CXCR4 chemotaxis and marks cells moving through epithelial-mesenchymal transition, and antibodies bound to it are internalised to lysosomes.
- Where found: Placental trophoblast: the tissue in which it was discovered; Many carcinomas, including colorectal, pancreatic, lung and breast, with low expression in most normal adult tissue; Mesothelioma: 10 of 12 cell lines and most biopsy specimens positive, with variable intensity; Advanced prostate cancer, including neuroendocrine and castration-resistant forms (systematic review 2026)

## Sources

- HGNC: TPBG gene record (HGNC:12004): https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12004
- He et al., EJNMMI 2025: [68Ga]Ga-NOTA-H006 preclinical and pilot clinical study (PMID 39377811): https://pubmed.ncbi.nlm.nih.gov/39377811/
- Liang et al., J Med Chem 2026: [89Zr]Zr-DFO-HB5 immuno-PET and 161Tb vs 177Lu therapy in colorectal cancer (PMID 41984171): https://pubmed.ncbi.nlm.nih.gov/41984171/
- Kong et al., Mol Pharm 2025: [18F]AlF-RESCA-H006 for pancreatic adenocarcinoma (PMID 40443260): https://pubmed.ncbi.nlm.nih.gov/40443260/
- Shapiro et al., Invest New Drugs 2017: first-in-human anti-5T4 ADC PF-06263507 (PMID 28070718): https://pubmed.ncbi.nlm.nih.gov/28070718/
- Harbi et al., EJNMMI Res 2026: oncofetal surface antigens in prostate cancer and radioligand targeting (PMID 41832388): https://pubmed.ncbi.nlm.nih.gov/41832388/
- ClinicalTrials.gov NCT06162988: PET imaging of 68Ga-NOTA-H006 in malignancy: https://clinicaltrials.gov/study/NCT06162988

## Connected records

- technologies: [Immuno-PET](https://nuclide.cc/technologies/immuno-pet/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/)
- isotopes: [Fluorine-18](https://nuclide.cc/isotopes/f-18/), [Gallium-68](https://nuclide.cc/isotopes/ga-68/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/), [Terbium-161](https://nuclide.cc/isotopes/tb-161/), [Zirconium-89](https://nuclide.cc/isotopes/zr-89/)
- targets: [CEACAM5](https://nuclide.cc/targets/ceacam5/), [Glypican-3](https://nuclide.cc/targets/gpc3/), [TROP2](https://nuclide.cc/targets/trop2/)
- indications: [Colorectal cancer](https://nuclide.cc/indications/colorectal-cancer/), [Metastatic castration-resistant prostate cancer](https://nuclide.cc/indications/prostate-mcrpc/), [Neuroendocrine and small-cell prostate cancer](https://nuclide.cc/indications/prostate-nepc/), [Pancreatic ductal adenocarcinoma](https://nuclide.cc/indications/pancreatic-cancer/)

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