Claudiximab

Claudiximab is a chimeric monoclonal antibody directed against the endogenous antigen GC182 (Claudin 18/CLDN18) with potential immunostimulatory and antineoplastic activities. The monoclonal antibody is currently still being used experimentally in the therapy of adenocarcinomas of the gastrointestinal tract and pancreatic tumours.

When administered, claudiximab (zolbetuximab) binds specifically to claudin 18.2 (see below claudins). This leads to a triggering of the body's immune reaction. Cytotoxic T-lymphocytes (CTL) are developed, which are directed against claudin 18.2-expressing tumour cells. This causes a reduced tumor cell proliferation and apoptosis of the tumor cells.

Claudin 18 is a transmembrane protein that is located in apical regions of the cell, where it is part oftight-junctioncomplexes. The isoform 2 of claudin-18, CLDN 18.2, is physiologically expressed in the epithelial cells of the stomach mucosa. Claudin 18.2 is overexpressed in a large number of tumor cells.

This is also the case in gastric, pancreatic and esophageal cancer as well as in non-small cell lung cancer (NSCLC) and its metastases.

Together with occludin, claudins are an important structural element of tight junctions. In principle, the overexpression of claudin 18.2 does not yet provide any information that is useful for disease management. This refers to the fact that claudin 18.2 is not part of a cancer-related signaling pathway. Thus, the effect of anti-claudin 18.2 therapy can only be explained by an enhancement of antibody-dependent cellular cytotoxicity. Clinical studies will show whether the expression of claudin 18.2 is predictive for therapy with claudiximab.

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