To investigate potential cellular or
humoral elements that can effect amyloidolysis,
I developed a novel in vivo experimental
model in which 6-week-old Balb/c mice were injected s.c. with up to
200mg (~1% of the mouse’s body weight) of
crude human AL (amyloid) extracts.
The resulting "amyloidomas" disappeared
within a 2-week period. Histologic studies
revealed that no Congo red-positive material (characteristic of
amyloid) was present in any of the mouse organs and
that the regressing amyloidomas were extensively infiltrated by
neutrophils. In contrast, no resolution of the amyloid occurred in old
(>1 year) or immunocompromised (e.g. SCID and CD18-deficient)
animals. This process was markedly accelerated by the injection at a
contra-lateral site of certain anti-human
light chain monoclonal antibodies (MoAbs)
having specificity for an amyloid-related
epitope (as evidenced in vitro by ELISA, flow cytometry, and
Remarkably, when mice were treated with
such MoAbs, the induced amyloidomas
disappeared within 3 to 4 days. From these and other experiments, I
have posited that this phenomenon is immune-mediated and involves
opsonization of the fibrils by anti-amyloid antibodies and subsequent
degradation by activation neutrophils.
These observations form the basis of my proposed project that is
- Identify and develop anti-AL MoAbs;
- Test the capability of these reagents to accelerate resolution of the human amyloidomas in the experimental in vivoanimal model;
- Investigate immune-related factors that may effect removal of AL deposits.
The ultimate objective of my research is to determine whether this
form of immunotherapy would benefit patients with Al amyloidosis.