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Sequence variation in the monoclonal-antibody-U36-defined CD44v6 epitope
N L Van Hal1, G A Van Dongen, C B Ten Brink
1Department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Cancer Immunology, Immunotherapy : CII
|December 9, 1997
Summary
Monoclonal antibody U36 targets epican in head and neck cancer. Researchers found a common variant, glutamic acid at position 367, is crucial for antibody binding, correcting a prior sequencing error.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Monoclonal antibody (mAb) U36 targets epican, a CD44 splice variant, for head and neck squamous cell carcinoma (HNSCC) treatment.
- The U36 epitope is in the CD44v6 domain, with potential sequence variations impacting antibody-antigen interaction and tumor targeting.
Purpose of the Study:
- To investigate the affinity of mAb U36 for variant epitope sequences.
- To clarify the in vivo relevance of reported amino acid differences in the CD44v6 epitope.
Main Methods:
- cDNA cloning for antigen characterization.
- Tumor cell binding assays using synthetic peptides for competition.
- Analysis of amino acid variations (position 367 and 374) in the CD44v6 epitope.
Main Results:
- Glutamic acid at position 367 strongly competed with mAb U36 binding, indicating its importance.
- The previously described valine variant at position 367 is an in vivo artifact.
- Lysine at position 374 (allelic polymorphism) did not affect mAb U36 binding; no allelic imbalance was observed.
Conclusions:
- The in vivo CD44v6 epitope sequence recognized by mAb U36 contains glutamic acid at position 367.
- mAb U36 binding is not affected by allelic polymorphism at position 374.
- Accurate epitope characterization is crucial for optimizing antibody-based cancer therapies.