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A tight-junction protein normally hidden in the stomach lining that becomes exposed in gastric and pancreatic cancers.
CLDN18.2 is normally buried in tight junctions of gastric mucosa; malignant transformation exposes it on the cell surface. Zolbetuximab (Vyloy) is approved with chemotherapy in CLDN18.2-positive gastric cancer. ADCs (CMG901/AZD0901, XNW27011), CAR-T (satricabtagene autoleucel, CT041), and bispecifics are in late-stage development.
In plain words · A tight-junction protein normally hidden in the stomach lining that becomes exposed in gastric and pancreatic cancers.
Backbone ribbon from PDB 9V32. RCSB PDB 9V32. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
A tight-junction protein normally hidden in the stomach lining that becomes exposed in gastric and pancreatic cancers.
Splice isoform 18.2; expressed in ~30-40% of gastric/GEJ adenocarcinomas and a subset of pancreatic ductal adenocarcinoma.
16 products aim at Claudin 18.2: antibodies, antibody-drug conjugates, bispecific antibodies, cell therapies and other agents. 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 or amplification: 1 of 1 label readouts filed under it score protein level or gene copies (Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong)), so the medicines rely on the tumour carrying more of it than normal tissue. HPA CLDN18: RNA group enriched (lung 238 nTPM, stomach 1 684 nTPM); high antibody staining in 1 normal tissue; highest cancer staining ovarian cancer (4 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Gastric & gastro-oesophageal junction cancer, Pancreatic ductal adenocarcinoma); approvals of single-target medicines aimed at it also list Oesophageal cancer, not counted; Open Targets associates it with 1 specific cancer type at or above 0.5 (gastric adenocarcinoma). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong) label threshold; Human Protein Atlas CLDN18 tissue; Human Protein Atlas CLDN18 pathology; Open Targets ENSG00000066405 associations
First described 2001. Earliest sequence paper UniProt cites for the protein: Niimi et al, Mol. Cell. Biol, 2001, "Claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Splice isoform 18.2; expressed in ~30-40% of gastric/GEJ adenocarcinomas and a subset of pancreatic ductal adenocarcinoma.
RNA: group enriched (lung 238 nTPM, stomach 1 684 nTPM), detected in some normal tissues.
Medium: Lung.
RNA group enriched: Pancreatic Adenocarcinoma 178 pTPM, Stomach Adenocarcinoma 285 pTPM.
Medium only: glioma, testis cancer.
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 |
|---|---|---|---|---|
| Pancreatic ductal adenocarcinoma | 20-60% | IHC, any expression | Wide range across series | Wikipedia |
| Gastric & gastro-oesophageal junction cancer | 35-40% | IHC 2+/3+ in >=75% of cells (zolbetuximab definition) | SPOTLIGHT/GLOW screening | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
ASP2138 is an experimental bispecific antibody from Astellas Pharma Global Development in phase 3 trials for gastric & gastro-oesophageal junction cancer, aimed at Claudin 18.2 and CD3.
AZD4360 is an experimental antibody-drug conjugate from AstraZeneca in phase 2 trials for gastric & gastro-oesophageal junction cancer, biliary tract cancer and pancreatic ductal adenocarcinoma, aimed at Claudin 18.2.
AZD5863 is an experimental bispecific antibody from AstraZeneca in phase 2 trials for gastric & gastro-oesophageal junction cancer, pancreatic ductal adenocarcinoma and oesophageal cancer, aimed at Claudin 18.2 and CD3.
BDC-4182 is an experimental monoclonal antibody from Bolt Biotherapeutics in phase 2 trials for gastric & gastro-oesophageal junction cancer, aimed at Claudin 18.2.
IBI343 is an experimental investigational agent whose form is not stated in the registry from Innovent Biologics (Suzhou) in phase 3 trials for pancreatic ductal adenocarcinoma, aimed at Claudin 18.2.
LB4330 is an experimental fusion protein from L & L Bio, Ningbo, China in phase 2 trials, aimed at Claudin 18.2.
LCB02A is an experimental monoclonal antibody from LigaChem Biosciences in phase 2 trials, aimed at Claudin 18.2.
LM-302 is an experimental antibody-drug conjugate from LaNova Medicines Zhejiang in phase 3 trials for gastric & gastro-oesophageal junction cancer, aimed at Claudin 18.2.
M108 is an experimental monoclonal antibody from FutureGen Biopharmaceutical (Beijing) in phase 3 trials for gastric & gastro-oesophageal junction cancer, aimed at Claudin 18.2.
RC118-ADC is an experimental antibody-drug conjugate from RemeGen in phase 2 trials, aimed at Claudin 18.2.
Satricabtagene autoleucel (satri-cel) is the first CAR-T therapy approved for a solid tumour (gastric cancer), in China.
Sonesitatug vedotin is a Claudin 18.2 ADC in phase 3 for gastric cancer, licensed by AstraZeneca from KYM Biosciences.
Spevatamig is an experimental bispecific antibody from Phanes Therapeutics in phase 2 trials for gastric & gastro-oesophageal junction cancer, pancreatic ductal adenocarcinoma and biliary tract cancer, aimed at Claudin 18.2 and CD47.
TAC01-CLDN18.2 is an experimental TCR-T cell therapy from Triumvira Immunologics in phase 2 trials, aimed at Claudin 18.2.
XNW27011 is an experimental antibody-drug conjugate from Astellas Pharma Global Development in phase 2 trials for pancreatic ductal adenocarcinoma, non-small-cell lung cancer and ovarian cancer, aimed at Claudin 18.2.
Zolbetuximab is the first drug against Claudin 18.2, a protein exposed on stomach cancer cells. Added to chemotherapy it extends survival by two to three months; nausea is the price.
This is the trial behind the first approval of a CAR-T therapy for a solid tumour, in China. The gain in progression-free survival is real but measured in weeks, 15 percent of patients randomised to satri-cel never received it, and nearly every treated patient had cytokine release syndrome, so the trade-off is very different from CAR-T in blood cancers. Overall survival is not reported in the abstract.
Patients with newly diagnosed advanced stomach cancer should now have Claudin 18.2 tested alongside HER2, PD-L1 and mismatch repair, because roughly a third will be eligible for zolbetuximab, which adds about three months of median survival. The main practical problem is nausea and vomiting during infusions, which needs aggressive prophylaxis. How to sequence or combine it with immunotherapy in PD-L1-positive tumours is unresolved.
Query for this target: (TITLE:"Claudin 18.2" OR ABSTRACT:"Claudin 18.2" OR TITLE:"CLDN18" OR ABSTRACT:"CLDN18") 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 Claudin 18.2, not a curated reading list.
Shares Metastatic pancreatic ductal adenocarcinoma, CAR-T cell therapy, Pancreatic ductal adenocarcinoma and the tags adc-target, car-t-target.
Shares Antibody-drug conjugate (ADC) and the tags adc-target, 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 Antibody-drug conjugate (ADC), Pancreatic ductal adenocarcinoma and the tag adc-target.
Shares CAR-T cell therapy and the tag car-t-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.
Shares Antibody-drug conjugate (ADC) and the tag adc-target.