Abstract B028: Claudin-18 expression (using the 43-14A antibody kit) in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for immunotherapy with zolbetuximab
Notice bibliographique
Résumé
Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy; despite efforts to improve outcomes, five-year survival remains below 15% and immunotherapies have largely been unsuccessful. Claudin-18.2 (CLDN18.2), overexpressed in some gastro-intestinal cancers, including PDAC, has emerged as a promising therapeutic target. Zolbetuximab, a monoclonal antibody targeting CLDN18.2, triggers antibody- and complement-dependent cytotoxicity. Zolbetuximab has demonstrated therapeutic benefit in locally advanced and metastatic gastric and gastroesophageal junction cancers in phase 3 clinical trials (SPOTLIGHT and GLOW). A phase 2 clinical trial of zolbetuximab for PDAC patients is underway, with patient eligibility dependent on the expression of CLDN18 in ≥75% of tumor cells. CLDN18 overexpression in PDAC has been reported in research studies using a variety of antibodies, methods, and positivity thresholds. However, minimal population-based expression data uses the 43-14A diagnostic kit from the zolbetuximab clinical trials. The 43-14A antibody will likely become the standard clinical companion diagnostic if PDAC therapeutic trials succeed; hence, understanding its utility for binding and clinical assessment is prescient. Herein, we report the expression of CLDN18 using the 43-14A antibody kit in a retrospective Atlantic Canadian cohort of patients with PDAC. Methods: Immunohistochemical staining of CLDN18 was performed using the 43-14A antibody on PDAC samples (n=121) collected from patients who underwent surgical resection between 2012 and 2024 in Nova Scotia. Formalin-fixed paraffin-embedded samples were stained by immunohistochemistry with the 43-14A clone, prediluted kit, according to the kit manufacturer’s recommended protocol on the recommended platform (Benchmark ULTRA), consistent with methods employed in clinical trials. A board- certified pathologist, blinded to clinical outcomes, assessed CLDN18 immunostaining. Tumor cell staining proportion and membranous intensity were evaluated, with positive cases defined as ≥ 75% of tumor cells exhibiting membranous staining with an intensity of ≥ 2. Results: Out of 121 PDAC tumors, 39 (32.2%) stained positive for CLDN18. Although no significant associations were identified between CLDN18 positivity and various clinical variables, there was a trend suggesting a potential correlation with lower tumor grade (p = 0.0738). The study was adequately powered to detect significant associations. Conclusions: Our findings indicate that 32.2% of PDAC tumors in this cohort are positive for CLDN18, suggesting that a significant proportion of patients in our population could benefit from zolbetuximab and other CLDN18.2 targeted immunotherapies. Citation Format: Riley J Arseneau, Emma Kempster, Carley Bekkers, Thomas Sampson, Boris L Gala-Lopez, Ravi Ramjeesingh, Jeanette E Boudreau, Thomas Arnason. Claudin-18 expression (using the 43-14A antibody kit) in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for immunotherapy with zolbetuximab [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B028.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».