GCI Discovery: Potential for Antibody-Drug Conjugates

During colorectal cancer (CRC) awareness month, we are highlighting recently published research from the Rosalind and Morris Goodman Cancer Institute (GCI) that aims to improve therapies for CRC patients.

Colorectal cancer is the 4^th most commonly diagnosed cancer in Canada, and a leading cause of cancer mortality. As CRC progresses, it often metastasizes (spreads) to the liver to cause poor outcomes for patients. Research in the Siegel lab at the GCI has focused on a protein called Claudin-2, which is present at high levels on the surface of CRC cells and promotes their invasion of the liver. Characterization of Claudin-2 in cancer has revealed it to be an attractive target for antibody-based therapeutics.

Antibodies are proteins that recognize highly specific targets and bind to them. They have emerged as a promising cancer therapy because they can bind and block the function of cancer promoting proteins like Claudin-2. Antibody-drug conjugates take the targeting power of antibodies even further, combing them with drugs that are delivered specifically to cancer cells that express the target. Through antibody-drug conjugates, toxic payloads such as chemotherapy drugs can be directed to cancer cells while sparing healthy cells.

Scientists in the Siegel lab generated antibodies targeting Claudin-2, which they then combined with potent chemotherapy drugs. Testing the antibody-drug conjugates showed they could impair the growth of CRC cells and reduce CRC liver metastasis in mice. Currently, the researchers are aiming to experiment with different drug payloads to create a second generation of even more effective Claudin-2 targeted antibody-drug conjugates.

These findings highlight the potential of Claudin-2 targeted antibody-drug conjugates as a promising therapy for CRC patients with liver metastases. By refining these therapies with optimized drug payloads, researchers at the GCI aim to develop more effective treatments that selectively target cancer cells while minimizing harm to healthy tissue. Pursuing these innovating treatment strategies is part of our quest to improve outcomes for those affected by colorectal cancer and find the #knowledgetocure.

The study, led by research associate Sébastien Tabariès in the Siegel laboratory, was a collaborative effort including researchers from the National Research Council Canada (direct by Dr. Anna Moraitis). To learn more, read the publication “Anti-Claudin-2 Antibody–Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis”.

Images were partly created using figures provided by Servier Medical Art (https://smart.servier.com/), licensed under a Creative Commons Attribution 4.0 License.