{"entity":{"id":"cldn18-2","kind":"target","name":"Claudin 18.2","aka":[],"tldr":"A tight-junction protein normally hidden in the stomach lining that becomes exposed in gastric and pancreatic cancers.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CLDN18","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CLDN18"}],"tags":["adc-target","car-t-target"],"related":["cldn6","cldn18-2-expression"],"cancers":["gastric","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":["lm-302","asp2138","m108","ibi343","xnw27011","azd4360","tac01-cldn18-2","lcb02a","rc118-adc","bdc-4182","lb4330","spevatamig","azd5863"],"companies":["xilio-therapeutics"],"institutions":[],"pathways":["gastric-cancer-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CLDN18","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e7695a21-abb6-47ac-93f8-0ece5a9c4409","note":">= 75% of tumour cells with moderate to strong membranous staining"},{"label":"Human Protein Atlas CLDN18 tissue","url":"https://www.proteinatlas.org/ENSG00000066405-CLDN18/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas CLDN18 pathology","url":"https://www.proteinatlas.org/ENSG00000066405-CLDN18/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000066405 associations","url":"https://platform.opentargets.org/target/ENSG00000066405/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:2039","ensembl":"ENSG00000066405","uniprot":"P56856","entrez":"51208","firstDescribed":2001,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/11585919/","biology":"Splice isoform 18.2; expressed in ~30-40% of gastric/GEJ adenocarcinomas and a subset of pancreatic ductal adenocarcinoma.","whereFound":["Gastric/GEJ adenocarcinoma","Pancreatic ductal adenocarcinoma","Biliary"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"gastric","pct":"35-40","measure":"IHC 2+/3+ in >=75% of cells (zolbetuximab definition)","source":"https://en.wikipedia.org/wiki/Zolbetuximab","note":"SPOTLIGHT/GLOW screening"},{"cancerId":"pancreatic","pct":"20-60","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/CLDN18","note":"Wide range across series"}]},"route":"/targets/cldn18-2/","neighbours":{"target":[{"id":"cldn6","kind":"target","name":"Claudin 6","route":"/targets/cldn6/"}],"biomarker":[{"id":"cldn18-2-expression","kind":"biomarker","name":"Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong)","route":"/biomarkers/cldn18-2-expression/"}],"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"gastric-cldn18-2-positive","kind":"cancer","name":"Claudin 18.2-positive gastric cancer","route":"/cancers/gastric-cldn18-2-positive/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","route":"/cancers/oesophageal-adenocarcinoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"asp2138","kind":"drug","name":"ASP2138","route":"/drugs/asp2138/"},{"id":"azd4360","kind":"drug","name":"AZD4360","route":"/drugs/azd4360/"},{"id":"azd5863","kind":"drug","name":"AZD5863","route":"/drugs/azd5863/"},{"id":"bdc-4182","kind":"drug","name":"BDC-4182","route":"/drugs/bdc-4182/"},{"id":"ibi343","kind":"drug","name":"IBI343","route":"/drugs/ibi343/"},{"id":"lb4330","kind":"drug","name":"LB4330","route":"/drugs/lb4330/"},{"id":"lcb02a","kind":"drug","name":"LCB02A","route":"/drugs/lcb02a/"},{"id":"lm-302","kind":"drug","name":"LM-302","route":"/drugs/lm-302/"},{"id":"m108","kind":"drug","name":"M108","route":"/drugs/m108/"},{"id":"rc118-adc","kind":"drug","name":"RC118-ADC","route":"/drugs/rc118-adc/"},{"id":"satricabtagene-autoleucel","kind":"drug","name":"Satricabtagene autoleucel","route":"/drugs/satricabtagene-autoleucel/"},{"id":"cmg901","kind":"drug","name":"Sonesitatug vedotin","route":"/drugs/cmg901/"},{"id":"spevatamig","kind":"drug","name":"Spevatamig","route":"/drugs/spevatamig/"},{"id":"tac01-cldn18-2","kind":"drug","name":"TAC01-CLDN18.2","route":"/drugs/tac01-cldn18-2/"},{"id":"xnw27011","kind":"drug","name":"XNW27011","route":"/drugs/xnw27011/"},{"id":"zolbetuximab","kind":"drug","name":"Zolbetuximab","route":"/drugs/zolbetuximab/"}],"company":[{"id":"keymed","kind":"company","name":"Keymed Biosciences (KYM Biosciences)","route":"/companies/keymed/"},{"id":"xilio-therapeutics","kind":"company","name":"Xilio Therapeutics","route":"/companies/xilio-therapeutics/"}],"pathway":[{"id":"gastric-cancer-signalling","kind":"pathway","name":"Gastric cancer (KEGG map)","route":"/pathways/gastric-cancer-signalling/"}],"trial":[{"id":"clarity-gastric01","kind":"trial","name":"CLARITY-Gastric 01","route":"/trials/clarity-gastric01/"},{"id":"nct04581473","kind":"trial","name":"CT041-ST-01","route":"/trials/nct04581473/"},{"id":"spotlight-glow","kind":"trial","name":"SPOTLIGHT & GLOW","route":"/trials/spotlight-glow/"}],"pairing":[{"id":"cldn18-antibody-then-adc","kind":"pairing","name":"CLDN18.2 antibody first line → CLDN18.2 ADC or CAR-T on progression","route":"/pairings/cldn18-antibody-then-adc/"}],"idea":[{"id":"idea-biomarker-quadruplet-gastric","kind":"idea","name":"Biomarker-directed first-line quadruplets in gastric cancer","route":"/ideas/idea-biomarker-quadruplet-gastric/"},{"id":"idea-in-vivo-car-solid","kind":"idea","name":"In vivo CAR-T against solid-tumour antigens","route":"/ideas/idea-in-vivo-car-solid/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"}],"person":[{"id":"qi-changsong","kind":"person","name":"Changsong Qi","route":"/people/qi-changsong/"},{"id":"lee-jeeyun","kind":"person","name":"Jeeyun Lee","route":"/people/lee-jeeyun/"},{"id":"shitara-kohei","kind":"person","name":"Kohei Shitara","route":"/people/shitara-kohei/"},{"id":"shen-lin","kind":"person","name":"Lin Shen","route":"/people/shen-lin/"},{"id":"ryu-min-hee","kind":"person","name":"Min-Hee Ryu","route":"/people/ryu-min-hee/"},{"id":"kang-yoon-koo","kind":"person","name":"Yoon-Koo Kang","route":"/people/kang-yoon-koo/"},{"id":"zev-wainberg","kind":"person","name":"Zev A. Wainberg","route":"/people/zev-wainberg/"},{"id":"li-zonghai","kind":"person","name":"Zonghai Li","route":"/people/li-zonghai/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"}],"paper":[{"id":"paper-ct041-st-01-lancet-2025","kind":"paper","name":"Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial","route":"/key-papers/paper-ct041-st-01-lancet-2025/"},{"id":"paper-spotlight-lancet-2023","kind":"paper","name":"SPOTLIGHT: zolbetuximab, the first Claudin 18.2 antibody, added to chemotherapy in gastric cancer","route":"/key-papers/paper-spotlight-lancet-2023/"}],"institution":[{"id":"ncc-hospital-east","kind":"institution","name":"National Cancer Center Hospital East","route":"/institutions/ncc-hospital-east/"},{"id":"pku-cancer-hospital","kind":"institution","name":"Peking University Cancer Hospital","route":"/institutions/pku-cancer-hospital/"}]}}