5T4 (trophoblast glycoprotein)
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
A heavily glycosylated leucine-rich-repeat membrane protein shared by trophoblast and cancer cells.
- 3 · How drugs use it
No product in this corpus aims at 5T4 (trophoblast glycoprotein) yet. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
External identifiers
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.
- 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)
Latest papers
topQuery for this target: (TITLE:"5T4" OR ABSTRACT:"5T4" OR TITLE:"trophoblast glycoprotein" OR ABSTRACT:"trophoblast glycoprotein" OR TITLE:"TPBG" OR ABSTRACT:"TPBG" OR TITLE:"5T4 oncofetal antigen" OR ABSTRACT:"5T4 oncofetal antigen" OR TITLE:"WAIF1" OR ABSTRACT:"WAIF1") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about 5T4 (trophoblast glycoprotein), not a curated reading list.
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