V. Bellotti et al., APPLICATION OF MONOCLONAL ANTIIDIOTYPES IN THE STUDY OF AL AMYLOIDOSIS - THERAPEUTIC IMPLICATIONS, Renal failure, 15(3), 1993, pp. 365-371
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.