Integral Molecular Reveals Mechanism Underlying Exquisite Specificity of Claudin 6 Therapeutic Antibody Being Developed for Solid Tumors

Excerpt from the Press Release:

PHILADELPHIA–Integral Molecular, the industry leader in antibody discovery for membrane proteins, has published the targeting mechanism enabling best-in-class specificity of its Claudin 6 (CLDN6) antibody CTIM-76 being developed for cancer therapy with Context Therapeutics. CLDN6 is a tumor-specific protein found in multiple solid tumors—including ovarian, endometrial, lung, gastric, and testicular—but absent from healthy adult tissues. Until now, its structural complexity and similarity to related proteins has hindered efforts to develop safe and selective therapeutics, with most CLDN6 antibody clinical trials being halted due to specificity-related safety issues. The similarity of the target to widely expressed Claudins 3, 4 and 9 means that non-specific binding could kill otherwise healthy tissues.

Publication Details
In their recent publication (Screnci et al., iScience December 2022), Integral Molecular scientists describe the isolation of highly specific CLDN6 antibodies that use a single atomic contact point centered around amino acid 156 to derive exquisite specificity. This interaction site allows the antibody to bind CLDN6 but not any of the other 24 claudin family members.

Key findings include:

• Best-in-class specificity of CLDN6 antibodies compared to clinical benchmarks
• Unusual steric hindrance mechanism of the gamma carbon on Q156 discovered as critical for absolute specificity of antibodies for CLDN6 versus CLDN9
• CLDN6 antibodies exhibited excellent developability

“We are thrilled to be progressing high-specificity antibodies to safely target Claudin 6-positive tumors,” said Ross Chambers, PhD, VP of Antibody Discovery at Integral Molecular.

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