Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand.
Myelin-specific T lymphocytes are considered essential in the pathogenesis of multiple sclerosis. The myelin basic protein peptide (a.a. 83-99) represents one candidate antigen; therefore, it was chosen to design an altered peptide ligand, CGP77116, for specific immunotherapy of multiple sclerosis. A magnetic resonance imaging-controlled phase II clinical trial with this altered peptide ligand documented that it was poorly tolerated at the dose tested, and the trial had therefore to be halted. Improvement or worsening of clinical or magnetic resonance imaging parameters could not be demonstrated in this small group of individuals because of the short treatment duration. Three patients developed exacerbations of multiple sclerosis, and in two this could be linked to altered peptide ligand treatment by immunological studies demonstrating the encephalitogenic potential of the myelin basic protein peptide (a.a. 83-99) in a subgroup of patients. These data raise important considerations for the use of specific immunotherapies in general.
Bielekova
B
B
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1400, USA.
Goodwin
B
B
Richert
N
N
Cortese
I
I
Kondo
T
T
Afshar
G
G
Gran
B
B
Eaton
J
J
Antel
J
J
Frank
J A
JA
McFarland
H F
HF
Martin
R
R
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D003429:Cross Reactions; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D017211:Treatment Failure
C415587:CGP 77116; D016207:Cytokines; D008024:Ligands; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; C104448:myelin basic protein 83-99