Untitled - D Ank Unlimited

chronic graft vasculopathy 170 chronic lymphocytic leukemia (CLL)
LTR CRD
Transfect engineered
retroviral vector,
carrying CGD gene,
into packaging cell line
Collect “virus”-laden
supernatant from
packaging cells
chronic graft vasculopathy
Smooth muscle cell proliferation in arteries or arterioles of
a graft induced by growth factors and cytokines released
from recipient T cells activated by allorecognition that
stimulate monocytes/macrophages in the graft and endothelial
cells in blood vessel walls to release these substances.
Narrowing of the graft vasculature leads to ischemia.
chronic granulomatous disease (CGD)
An immunodeficiency disorder that is inherited as an
X-linked trait in two thirds of the cases and as an autosomal-recessive
trait in the remaining third. Clinical features
are usually apparent before the end of the second year of
life. An enzyme defect is associated with NADPH oxidase.
This enzyme deficiency causes neutrophils and monocytes
to have decreased consumption of oxygen and diminished
glucose utilization by the hexose monophosphate shunt.
Although neutrophils phagocytize microorganisms, they do
not form superoxide and other oxygen intermediates that
usually constitute the respiratory burst. Neutrophils and
monocytes also form a smaller amount of hydrogen peroxide,
have decreased iodination of bacteria, and have diminished
production of superoxide anions. All of this leads to
decreased intracellular killing of bacteria and fungi. Thus,
these individuals have increased susceptibility to infection
Collect peripheral blood
progenitor cells from patient
Combine for transduction
of progenitor cells with
CGD-carrying “virus”
Inject “corrected” progenitor
cells back into patient,
Superoxide is produced,
CGD is treated.
Strategy for gene therapy in chronic granulomatous disease (CGD) with peripheral blood progenitor cells.
with microorganisms that normally are of relatively low
virulence. These include Aspergillus spp., Serratia marcescens,
and Staphylococcus epidermidis. Patients may have
hepatosplenomegaly, pneumonia, osteomyelitis, abscesses,
and draining lymph nodes. The quantitative nitroblue tetrazolium
(NBT) test and the quantitative killing curve are
both employed to confirm the diagnosis. Most microorganisms
that cause difficulty in CGD individuals are catalasepositive.
Therapy includes interferon-γ, antibiotics, and
surgical drainage of abscesses.
chronic lymphocytic leukemia (CLL)
A peripheral B cell neoplasm in which the peripheral blood
is flooded with small lymphocytes exhibiting condensed
chromatin and scant cytoplasm. Disrupted tumor cells
termed smudge cells represent a characteristic finding.
Most patients have absolute lymphocyte counts above 4000/
mm 3 of blood. CLL is the most common leukemia of adults
in the Western world. The tumor cells resemble a small
subset of circulating B cells that express the surface marker
CD45. The tumor cells express CD5, as well as the pan-B
cell markers CD19 and CD20. However, they fail to express
CD10. There is dim surface expression of immunoglobulin
D heavy chain, and either κ or λ light chain chromosomal
anomalies include trisomy 12 deletions of 13q 12–14 and