|Professor Michael Sela|
The W. Garfield Weston Professor of Immunology
Myasthenia Gravis, Multiple Sclerosis and Antibodies to ErbB Receptors
A peptide composed of analogs to two myasthenogenic T cell epitopes is capable of immunomodulating in vitro and in vivo autoimmune T-cell responses and to reverse experimental MG in mice, even when it is induced by the complete acetylcholine receptor of the Torpedo fish and given orally. This is due to T-cell receptor antagonism. The altered peptide inhibits the activities of matrix metalloproteinase-9 and phospholipase c and inhibits T-cell interaction with VCAM-1 induced in vivo by a myasthenogenic T cell epitope. Phase I clinical trial is in the planning (with Prof. Edna Mozes1).
Cop 1, the synthetic copolymer developed in our laboratory, is clinically beneficial in multiple sclerosis (MS). Secretion of Th2 cytokines after exposure to either Cop 1 or MBP lends support to the "bystander" suppression by Cop 1 of EAE. Oral administration of Cop 1 suppresses efficiently EAE. Specific ThTh2 cells accumulate in the central nervous system of mice protected against EAE by Cop 1 (with Prof. Ruth Arnon2).
ErbB-2 is an orphan receptor that belongs to tyrosine kinase receptors for either epidermal growth factor (EGF) or Neu differentiation factor (NDF). One group of tumor-inhibitory mAbs inhibited binding of NDF and EGF to their direct receptors, due to acceleration of ligand dissociation. Antibody-induced therapy may be due to the blocking of heterodimerization between ErbB-2 and growth factor receptors. c-Cbl is a suppressor of the Neu oncogene (with Prof. Yossi Yarden3).
1with Prof. Mozes: Dr. Miri Paaz-Rozner, Dr. Jianping Liu, Dr. Molly Dayan.
2with Prof. Arnon: Dr. Dvora Teitelbaum, Dr. Rina Aharoni, Ada Veksler.
3with Prof. Yarden: Dr. Bilha Schechter, Lilach Friedman).
List of Publications (last 3 years)
Complete List of Publications