CLDN6: An Emerging Role in Cancer

Various claudin (CLDN) family members are located at tight junctions between epithelial cells. Abnormal expression of CLDN6 can serve multiple roles in the occurrence and development of tumours. As a member of the claudins family, CLDN6 is considered to be the next "New Favorite" in targeted cancer therapy after CLDN18. CLDN6 can be involved in the development and progression of many malignant tumors such as breast cancer, gastric cancer, and Hepatocellular carcinoma (HCC). Based on CLDN6's spatial structure and regulatory characteristics, exploring or designing CLDN6-targeted drugs to actively regulate CLDN6 related signaling molecules and interfere with tumor progression is of great value for the early diagnosis and precise treatment of tumors.

Fig. 1 Structure diagram of CLDNs and molecular diagram of CLDN6. (Du H.; et al. Mol Med Rep. 2021)

Prospect of CLDN6 in the treatment of tumours

CLDN6 expression is associated with the patient prognosis of a variety of tumors. It is studied to be used for emerging immunotherapies to treat cancers including monoclonal antibodies, bispecific antibodies (BsAbs), antibody–drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapy.

• Monoclonal Antibodies
  The use of CLDN6 antibody can block tumour growth and prolong the life of patients with TGCT. The presence of tumour-associated antigens can induce strong and persistent antigen-specific T-cell responses, break the immune system tolerance to endogenous self-antigens and produce effective anti-tumour effects.
• BsAbs
  T cell engaging bispecific antibodies (TCE) are potent tumor-targeting agents that act by linking a patient's T cells to proteins expressed on a cancer cell surface to create an augmented recognition that allows the T cells to kill the cancer cells. 6PHU3, a T-cell-engaging bispecific single-chain molecule (bi-(scFv)2) with anti-CD3/anti-CLDN6 specificities, is highly specific and efficient for the treatment of CLDN6-positive solid cancers
• ADCs
  The antibodies used by ADCs have high specificity for tumour cell surface proteins and can specifically kill tumour cells. Anti-CLDN6 monoclonal antibody conjugated with cytotoxic agent (Mertansine) DM1 (CLDN6-DM1) was developed and showed preclinical antitumor activity in HCC treatment. In addition, IMAB027-VCMMAE offers a very effective destruction of the target cells by activating bystander cell killing of heterologous expression of human CLDN6 xenograft tumors.
• CAR-T
  CAR-T cells can be used to treat tumours expressing chimeric antigen receptors after the gene transformation of B-cell malignant tumours. CLDN6 is an ideal expression profile for CAR-T cells targeting as a strictly oncofetal cell surface antigen.

Creative Diagnostics provides a series of antibodies, antigens and kits against CLDN6 to assist our global customers in their preclinical and clinical safety/efficacy testing. Please browse our list for specific products.