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Glypican-3 is a fetal liver protein that reappears in liver cancer, giving CAR-T and bispecifics a clean target.
Glypican-3 is a heparan sulfate proteoglycan that modulates Wnt and Hedgehog signalling; it is a fetal liver protein expressed in 70-80% of hepatocellular carcinoma and essentially absent from normal adult liver, which gives cell and bispecific therapies a clean target. It is also found in hepatoblastoma and yolk-sac tumours. Antibodies failed as monotherapy (codrituzumab), suggesting that simply binding GPC3 is not enough. GPC3 CAR-T, including armoured constructs from AstraZeneca/Neogene and Chinese groups, and GPC3×CD3 bispecifics are showing responses, though durability and the hostile liver microenvironment remain concerns. The simple version is a liver-development protein that reappears in liver cancer, letting engineered immune cells recognise the tumour.
In plain words · Glypican-3 is a fetal liver protein that reappears in liver cancer, giving CAR-T and bispecifics a clean target.
Glypican-3 is a fetal liver protein that reappears in liver cancer, giving CAR-T and bispecifics a clean target.
Glypican-3 is a heparan sulfate proteoglycan modulating Wnt and Hedgehog signalling.
1 product aims at Glypican-3: bispecific antibodies. 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.
Tumour-associated overexpression: 1 cell-killing or cell-finding medicine (AZD9793) aim at the antigen, which HPA finds with no normal tissue stained high; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA GPC3: RNA tissue enriched (placenta 670 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Hepatocellular carcinoma); Open Targets associates it with 1 specific cancer type at or above 0.5 (Wilms tumor 1). (Rule 5 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas GPC3 tissue; Human Protein Atlas GPC3 pathology; Open Targets ENSG00000147257 associations
First described 1996. Earliest sequence paper UniProt cites for the protein: Pilia et al, Nat. Genet, 1996, "Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome". Source.
Glypican-3 is a heparan sulfate proteoglycan modulating Wnt and Hedgehog signalling.
RNA: tissue enriched (placenta 670 nTPM), detected in many normal tissues.
No normal tissue stained high.
RNA cancer enhanced: Liver Hepatocellular Carcinoma 291 pTPM.
No cancer sample stained medium or high.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Hepatocellular carcinoma | 70-80% | IHC, any expression | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AZD9793 is an experimental T-cell engager from AstraZeneca in phase 2 trials for hepatocellular carcinoma, aimed at Glypican-3.
Query for this target: (TITLE:"Glypican-3" OR ABSTRACT:"Glypican-3" OR TITLE:"GPC3" OR ABSTRACT:"GPC3") AND (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 Glypican-3, not a curated reading list.
Shares CAR-T cell therapy and the tag car-t-target.
Shares CAR-T cell therapy and the tag car-t-target.
Shares Zonghai Li, In vivo CAR-T against solid-tumour antigens, Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR, CAR-T cell therapy and the tag car-t-target.
Shares Zonghai Li, CAR-T cell therapy and the tag car-t-target.
Shares CAR-T cell therapy and the tag car-t-target.
Shares AZD9793, Hepatocellular carcinoma.
Shares Zonghai Li, CAR-T cell therapy, Hepatocellular carcinoma.
Shares Zonghai Li, In vivo CAR-T against solid-tumour antigens, Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR, CAR-T cell therapy.