Claudin 6
Claudin 6 is a Compelling Therapeutic Target
Claudin 6 (CLDN6) is an oncofetal protein, which is considered a favorable target candidate for immunotherapy. CLDN6 is normally present at higher levels during embryonic development, and then in normal, healthy adult tissues is turned off or is associated with low levels of expression.
Increased expression of these antigens can occur in some tumor cells, and are referred to as “tumor-associated antigens” or TAA. CLDN6 is considered a promising tumor-associated antigen given its enrichment in cancer cells versus normal, healthy cells.
CLDN6 is Expressed in a Wide Range of Tumors
The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. CLDN6 expression was evaluated in the TCGA dataset across a wide range of cancers (McDermott 2023). Individual patient samples are depicted with box and whisker plots showing the median, 25th and 75th percentiles of expression. It is estimated that there are 70,000 patients with CLDN6-positive metastatic solid tumors in the United States, and no approved targeted treatment options exist.
Claudin 6 is Prognostic
5-Year Survival Rates
While many genes are upregulated in cancer cells, there is not always a correlation between upregulation and oncogenic drive. Therefore, it is critical to identify genes that have a correlation with cancer and patient prognosis. Claudin 6 has been shown to be an independent prognostic marker across numerous cancers, including endometrial, bladder, and stomach.
For example, high CLDN6 expression is associated with worse overall survival in patients with endometrial cancer (Kojima 2020). The 5-year survival rates in the high (red line) and low (black line) CLDN6 groups was approximately 30% and 90%, respectively.