Application of monoclonal anti-idiotypes in the study of AL amyloidosis: therapeutic implications.
A monoclonal anti-idiotyped antibody (IgG1k MAb 3B11D4) has been raised against the lambda-chain dimers isolated from the urine of a patient (DEP) with AL amyloidosis. This antibody binds a conformational idiotope present on the monoclonal DEP IgA, but does not recognize the reduced and alkylated lambda-chain monomers, nor the 15- to 17-kDa light chain fragments obtained from the amyloid fibrils, which have the same N-terminal sequence as the urinary light chains. The nonreactivity of this MAb with amyloid fibrils was confirmed by immunohistochemical examination of cryostatic sections of an amyloidoma surgically removed from the patient's subcutaneous tissue. Our data demonstrate that the deletion of about 70 amino acid residues of the C-terminus of the lambda chain prevents the formation of the self-limiting dimer and may facilitate the deposition of fragments into amyloid fibrils. With regard to the amyloidogenic clone, MAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning and cytotoxicity experiments demonstrate that this antibody has the capability of selectively eliminating the idiotype-positive cells from peripheral blood. Antibodies with these properties could find application in a new therapeutic strategy which provides high-dose chemotherapy, total body irradiation, and rescue with circulating stem cells. These antibodies could be used in two distinct phases: first, in the purging of the stem cells to be infused from the amyloidogenic clone and, secondly, in an attempt to eliminate residual disease by intravenous infusion.
Immunochemistry Laboratory, University Hospital IRCCS Policlinico S. Matteo, Pavia, Italy.
V
V
Bellotti
M
M
Stoppini
V
V
Perfetti
I
I
Zorzoli
G
G
Marinone
A
A
Maggi
R
R
Invernizzi
E
E
Arbustini
G
G
Merlini
D000682:Amyloid / Q000276:immunology; D000686:Amyloidosis / Q000276:immunology / Q000628:therapy*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D000682:Amyloid; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A