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Identification of Functional Protein Regions Through Chimeric Protein Construction
Published on: January 8, 2019
Identification and characterization of Ch806 mimotopes
Lin Yang1, Hua Jiang, Bizhi Shi
1Shanghai Medical College, Fudan University, No. 130, Dong'an Road, Shanghai, 200032, China.
Cancer Immunology, Immunotherapy : CII
|June 15, 2010
Summary
New peptide mimics can generate antibodies that target cancer-associated epidermal growth factor receptor (EGFR) variants. These mimotopes offer a potential alternative to passive antibody immunization for cancer therapy.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Chimeric antibody 806 (Ch806) targets cancer-specific epidermal growth factor receptor variant III (EGFRvIII) and overexpressed EGFR.
- Passive antibody immunization for Ch806 requires prolonged, repeated administration for effective antitumor titers.
Purpose of the Study:
- To develop novel epitope mimics for Ch806.
- To assess if these peptide mimics can induce similar antibody production through active immunization.
Main Methods:
- Utilized a phage display peptide library to identify mimotopes binding to mAb 12H23, which recognizes similar epitopes to Ch806.
- Conjugated identified mimotopes to carrier proteins (KLH) for immunization of BALB/c mice.
- Evaluated sera reactivity against EGFRvIII and overexpressed EGFR, and performed antibody-dependent cellular cytotoxicity (ADCC) assays.
Main Results:
- Two mimotopes (WHTEILKSYPHE and LPAFFVTNQTQD) successfully mimicked the Ch806 epitope.
- Sera from mimotope-immunized mice recognized recombinant/synthetic Ch806 epitope, overexpressed EGFR (A431 cells), and EGFRvIII (Huh7-EGFRvIII cells).
- Mimotope-induced antibodies demonstrated specific lysis of Huh-7-EGFRvIII cells in ADCC assays.
Conclusions:
- Identified peptide mimotopes can elicit antibodies that recognize cancer-related EGFR targets.
- These mimotopes represent potential alternative therapeutic agents for cancers expressing EGFRvIII or EGFR overexpression.
