Medicine› Oncology› Chemokine receptors and signaling

Inflammatory disease immunotherapy — Neutralising mouse antibodies against human CCR6

Submitted 2026-10-23

Field: Medicine › OncologyType: A method hit a wallArea: inflammatory disease immunotherapyTarget: Neutralising mouse antibodies against human CCR6Stage: preclinical

Hypothesis

Immunising mice with CCR6 peptides or CCR6-expressing cells would produce monoclonal antibodies that block the receptor from binding its ligand CCL20.

What failed

Peptide immunisation produced no antibodies that recognised the native receptor. Cell immunisation produced CCR6-specific antibodies, but none blocked CCL20 binding.

Broken assumption

Standard mouse immunisation can produce function-blocking antibodies against human CCR6.

Why

All the antibodies, including commercial ones, bound one dominant region at the start of the receptor that does not affect its function.

From the published paper: Dorgham et al. PLoS ONE, 2016. ↗CC BY

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Related failures (1)

Matched on shared genes, mechanisms and ways of failing as well as wording. Each shows why it matched — treat these as leads rather than verdicts.

b cell immunologyZBTB38 transcription factordifferent research area
ZBTB38, a transcription factor highly expressed in germinal centre B cells and plasma cells, would be needed for normal antibody responses, as related family members are.
Mice lacking ZBTB38 in blood cells had normal germinal centre B cell numbers, normal antibody responses after immunisation, and normal memory B cell recall. Very few genes changed in B cells without ZBTB38.
Why it matched: similar wording · failed the same way: Held in the model species, not beyond it

Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.