APPLICATION OF MONOCLONAL ANTIIDIOTYPES IN THE STUDY OF AL AMYLOIDOSIS - THERAPEUTIC IMPLICATIONS

Citation
V. Bellotti et al., APPLICATION OF MONOCLONAL ANTIIDIOTYPES IN THE STUDY OF AL AMYLOIDOSIS - THERAPEUTIC IMPLICATIONS, Renal failure, 15(3), 1993, pp. 365-371
Citations number
NO
Categorie Soggetti
Urology & Nephrology
Journal title
ISSN journal
0886022X
Volume
15
Issue
3
Year of publication
1993
Pages
365 - 371
Database
ISI
SICI code
0886-022X(1993)15:3<365:AOMAIT>2.0.ZU;2-M
Abstract
A monoclonal anti-idiotype 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 idioto pe present on the monoclonal DEP IgA, but does not recognize the reduc ed and alkylated lambda-chain monomers, nor the 15- to 17-kDa light ch ain fragments obtained from the amyloid fibrils, which have the same N -terminal sequence as the urinary light chains. The nonreactivity of t his MAb with amyloid fibrils was confirmed by immunohistochemical exam ination of cryostatic sections of an amyloidoma surgically removed fro m the patient's subcutaneous tissue. Our data demonstrate that the del etion of about 70 amino acid residues of the C-terminus of the lambda chain prevents the formation of the self-limiting dimer and may facili tate the deposition of fragments into amyloid fibrils. With regard to the amyloidogenic clone, MAb 3B11D4 recognizes the plasma cell clone i n bone marrow and 9% of circulating B lymphocytes. Panning and cytotox icity experiments demonstrate that this antibody has the capability of selectively eliminating the idiotype-positive cells from peripheral b lood. Antibodies with these properties could find application in a new therapeutic strategy which provides high-dose chemotherapy, total bod y irradiation, and rescue with circulating stem cells. These antibodie s could be used in two distinct phases: first, in the purging Of the s tem cells to be infused from the amyloidogenic clone and, secondly, in an attempt to eliminate residual disease by intravenous infusion.