Fight gastric cancer by targeting Claudin 18.2

Fight gastric cancer by targeting Claudin 18.2

 


Gastric cancer (GC) is one of the most common and the 3rd deadly cancers worldwide, with a high frequency of recurrence and metastasis, and a poor prognosis. Effective treatment of GC remains challenges. Claudin 18.2 is considered as a new therapeutic target for advanced gastric cancer.

 

The normal and aberrant expressions of Claudin 18.2

Claudins, a family of tight junction proteins, establish a paracellular barrier between cells. Their altered function has linked to cancer formation. Claudin 18.2 expression has been shown to have prognostic value in gastric cancer. Sahin et al. identified Claudin 18.2 isoform and observed its expression is restricted in differentiated epithelial cells of normal gastric mucosa, with an orthotopic expression in gastric cancers and its metastases. Furthermore, multiple studies reveal that Claudin 18.2 is aberrantly expressed in various tumors and metastases, including pancreatic, biliary, ovarian, and lung adenocarcinomas. The strictly limited expression in normal tissues but very stable expression in malignant tumors makes Claudin 18.2 a cancer biomarker and therapeutic target.

arigo offers an excellent Claudin 18.2 specific antibody which is the best solution for precise and efficient detection of Claudin 18.2 expression.

 

Claudin 18.2 antibody (ARG67014)

Claudin 18.1 predominantly expresses in lung whereas Claudin 18.2 displays stomach specificity.
This antibody specifically detects Claudin 18.2 in normal gastric tissue.

 

Claudin 18.2, an ideal anti-cancer target

Claudin 18.2 is a candidate target for cancer therapy as it participates in proliferation, differentiation and migration of tumor cells. In normal tissues, Claudin 18.2 had a basolateral rather than apical tight junction localization in gastric epithelial cells. While upon malignant transformation, the changes in cell polarity lead to cell surface exposure of Claudin 18.2 epitopes, which make Claudin 18.2 an attractive surface target for developing therapeutic antibodies.

 

Claudin 18.2 targeting therapy

Targeting Claudin 18.2 is a promising neo-approach for GC treatment as Claudin 18.2 is expressed in approximately 80% of GC. Multiple therapeutic agents targeting Claudin 18.2, including mAbs, bispecific antibodies, chimeric antigen receptor T (CAR-T) cells, and antibody-drug conjugates (ADCs), have been developed. At present, a monoclonal antibody and chimeric antigen receptor engineered T (CAR-T) cells targeting Claudin 18.2 show promising results in clinical trials.

 

Monoclonal antibodies targeting Claudin18.2

The clinical trials of several Claudin 18.2-targeted antibodies are ongoing. Zolbetuximab (IMAB362, claudixmab), the first developmental antibody-drug against Claudin 18.2, had been validated its ability to eliminate cancer cells in preclinical studies. Currently, Zolbetuximab is in phase III clinical trials for treating advanced/metastatic GC and advanced gastroesophageal junction (GEJ) cancer.

arigo offers the most sensitive M13 antibodies which are the best solutions to facilitate the screening of therapeutic antibodies by M13 phage display platform.

 

M13 g8p antibody [SQab21250] (ARG66892)

M13 g8p antibody [SQab21250] (HRP) (ARG66893)

 

CAR-T cells targeting Claudin 18.2

CAR-T-cell therapy is based on engineering of T lymphocytes to express chimeric antigen receptors (CARs), which enables the modified T lymphocytes to recognize and eliminate cancer cells. Early studies have explored the potential of Claudin 18.2-specific CAR T-cell therapy in GC and other cancers. The clinical efficacy and toxicity of multiple CAR-T-cell candidates are assessed by several phase I/II clinical trials.

As with CAR T-cell therapy in general, cytokine release syndrome (CRS) is a potential adverse effect that may make clinical application challenging. arigo offers the CRS Cytokine Multiplex ELISA Kit (ARG82969) which is the best solution to monitor the CAR-T induced CRS.

 

Human CAR-T / CRS Cytokine Multiplex ELISA Kit (ARG82969)

The kit allows a concurrent measurement of 4 key cytokines
IFNγ, IL-2, IL-6, and IL-10.