Identification of patient-specific peptides for detection of M-proteins and myeloma cells.
We have taken advantage of the selection power of phage display technology to define specific peptide mimotopes that recognize individual M-proteins, isolated from patients with multiple myeloma. Preferred amino acid motifs of phages binding to M-proteins were identified in 6/9 patients investigated. Chemically synthesized peptides, corresponding to the phage-displayed peptide inserts, were used to verify the specificity of binding in competition assays. The peptides were able to bind to the M-proteins, as well as the myeloma cells, with high sensitivity and specificity. Employing simple immunological techniques, < 0.01 g/l of M-protein could be quantified, suggesting a novel way for monitoring minimal residual disease in the production of guidelines for adjusting or reintroducing conventional chemotherapy. The peptide mimotopes defined by this technology may be useful as tumour-specific targeting agents and as a tool for purging cells in autologous bone marrow transplantation.
Szecsi
P B
PB
Clinical Biochemistry, Roskilde County Hospital, Roskilde, Denmark.
Riise
E
E
Roslund
L B
LB
Engberg
J
J
Turesson
I
I
Buhl
L
L
Schafer-Nielsen
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism; D064211:Connectin; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D009124:Muscle Proteins; D009194:Myeloma Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding
D064211:Connectin; D000939:Epitopes; D007074:Immunoglobulin G; D009124:Muscle Proteins; D009194:Myeloma Proteins; D010455:Peptides; C085016:multiple myeloma M-proteins; D016650:Fluorescein-5-isothiocyanate