0000000000681359
AUTHOR
Christoph Rohde
Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma.
CLDN18.2 expression is highly prevalent in Japanese patients with gastric cancer, making it a targetable alteration, and supporting development of zolbetuximab as a therapeutic agent for this patient population.
Claudin-18 gene structure, regulation, and expression is evolutionary conserved in mammals
Claudin-18 isoform 2 (CLDN18.2) is one of the few members of the human claudin family of tight junction molecules with strict restriction to one cell lineage. The objective of the current study was to compare molecular structure and tissue distribution of this gastrocyte specific molecule in mammals. We show here that the CLDN18.2 protein sequence is highly conserved, in particular with regard to functionally relevant domains in mouse, rat, rabbit, dog, monkey and human and also in lizards. Moreover, promoter regions of orthologs are highly homologous, including the binding site of the transcription factor cyclic AMP-responsive element binding protein (CREB), which is known to regulate acti…
A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer
Introduction IMAB362 (Zolbetuximab) is a chimeric monoclonal antibody that binds to Claudin-18.2, a target antigen specific to cancer cells. In vitro, IMAB362 mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity; thus, IMAB362 may serve as a potent, targeted immunotherapeutic agent. Methods This first-in-human phase I study enroled adult patients (N = 15) with advanced gastric or gastro-oesophageal junction cancer into five sequential single dose-escalation cohorts (33, 100, 300, 600, and 1000 mg/m2) following a 3 + 3 design. Safety/tolerability, including determination of maximum tolerated dose and recommended phase II dose, were the pr…
High Prevalence of Claudin 18.2 Expression in Japanese Patients with Gastric Cancer.
e15584 Background: Expression of the gastric mucosal tight junction protein, Claudin-18.2 (CLDN18.2), is altered in gastric cancer (GC). In a phase 2 clinical trial (NCT01630083; FAST), a monoclonal antibody against CLDN18.2 (IMAB362) significantly increased overall survival in European patients with CLDN18.2-positive (CLDN18.2+) gastric and gastroesophageal junction adenocarcinomas when added to an EOX chemotherapy regimen. As the GC occurrence is high in Japan, this study evaluated the prevalence of CLDN18.2 expression in Japanese patients with GC. Methods: CLDN18.2 expression was assessed in primary GC tumors and corresponding lymph node metastases (LNM) by cell membrane staining intens…