s
i
ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000056
M-protein Binding Peptides from Phage Display Libraries as
Biomarkers in Multiple Myeloma: a Paradigm for Early Detection
of Disease Relapse
Michael A. Firer
Department of Chemical Engineering & Biotechnology, Ariel University Center, Ariel, Israel
T
he detection of specific biomarkers with simple laboratory tests can may
important implications in the diagnosis, treatment and survival of patients. An
example is Multiple Myeloma (MM), an incurable B-cell leukemia. With the use
of new drugs, most MM patients now enter into a period of remission; however
they inevitably relapse. MM tumor cells derive from a single clone of plasma cells
that usually express and secrete excess amounts of clonotypic immunoglobulin
(M-protein). Within each patient, M-protein VH
gene sequences differ suggesting that
these antibodies are directed against different antigens. Currently, electrophoresis
and gel immunofixation are used to identify the presence and isotype of M-proteins
in serum, however these methods are both tedious and insensitive. Particularly with
regards to early intervention in patients in remission, a more sensitive method that
heralds the presence of the specific M-protein biomarker would indicate disease
relapse, leading to earlier resumption of treatment and potentially enhanced patient
survival. To this end, we have used phage display peptide libraries to isolate peptides
that bind M-proteins from MM patients. Bioinformatic analyses of the peptide
sequences determined their homology to natural proteins of clinical significance
including proteins from bacterial species associated with respiratory infections and
food poisoning. These peptides can then be conjugated to fluorescent or other
reporter molecules and used in simple immunoassays to follow the reappearance
of the patient's M-protein in serum. The isolation of biomarker-binding peptides and
their use in sensitive immunoassays is a platform approach that can be applied to
development of improved methods for the monitoring of patients.
ANALBIOANAL-2010
O
M
I
C
S
P
i
u
h
b
l
n
g
G
r
o
u
p