Integrative molecules reveal the specificity of Claudin 6 therapeutic antibodies for solid tumors

Integral Molecular, an industry leader in membrane protein antibody discovery, has released a targeting mechanism for its Claudin 6 (CLDN6) antibody ctm-76, which is being developed in collaboration with Context Therapeutics for cancer therapy
.
CLDN6 is a tumor-specific protein found in a variety of solid tumors, including the ovaries, endometrium, lungs, stomach, and testes, but not in
healthy adult tissues.
Until now, the complexity of its structure and similarity to related proteins has hampered efforts to develop safe and selective treatments, and most CLDN6 antibody clinical trials have been discontinued
due to specificity-related safety concerns.
The similarity of this target to widely expressed claudin 3, 4, and 9 means that nonspecific binding can kill otherwise healthy tissue
.

The scientists described the isolation of a highly specific CLDN6 antibody that uses a single atomic contact point centered on amino acid 156 to obtain precise specificity
.
This interaction site allows the antibody to bind to CLDN6, but not to
the other 24 claudin family members.

Key findings include:

• Optimal specificity of CLDN6 antibodies compared to clinical benchmarks

• The unusual steric steric hindrance mechanism of γ carbon on Q156 was found to be critical for the absolute specificity of CLDN6 and CLDN9 antibodies

• CLDN6 antibodies exhibit good development

Dr.
Ross Chambers, Vice President of Antibody Discovery at Integral Molecular, said: "We are excited to develop highly specific antibodies that can safely target Claudin 6-positive tumors
.
" The ability of our antibody to interact specifically with Claudin 6 is extraordinary because the target protein and related proteins differ by only a few atoms
at the binding site.
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