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Monoclonal Antibodies Medical Animation

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Monoclonal Antibodies - medical animation
A.CD23 as key marker
a.45-kDa transmembrane glycoprotein
b.Normally functions as the low-affinity IgE receptor
c.Highly expressed on B-CLL cells
d.Lumilixmab binds to CD23 expressed on the surface of target cells
e.Induces cell lysis through antibody-dependent, cell-mediated cytotoxicity ; complement-dependent
cytotoxicity; and apoptosis
f.Primary MOA is apoptosis
1.Via intrinsic/mitochondrial pathway
2.Cross-linking dependent
Galiximab
B.CD80 as key marker
a.Transmembrane glycoprotein constitutively expressed on malignant B cells and transiently
expressed on normal activated B cells and antigen-presenting cells
b.Expressed by nonmalignant cells (macrophages, etc) that are variably present in the tumor
microenvironment and possibly support disease progression in follicular NHL
c.Involved in activation and regulation of T cells
d.Mediates antidependent cellular activity (ADCC) in vitro
e.Galiximab binds well to CD80 on B-cell surface (also known as B7.1)
f.In NHL (and HL), CD80 is markedly overexpressed
g.CD80 target is found uniformly on reed-Sternberg cells—the malignant component of Hodgkin’s
disease—as well as in majority of non-Hodgkin’s lymphomas
h.ADCC-mediated killing of CD80 positive malignant B cells and inhibits tumor progression

Monoclonal Antibodies
C.CD20 antigen
a.Transmembrane protein expressed on B-cell CLLs
b.Not found on hematopoietic stem cells, pro-B cells, normal plasma cells, or other normal tissues
c.May function as a calcium ion channel
d.Regulates early steps in the activation process for cell-cycle initiation and differentiation
e.A stable target that does not shed, modulate, or internalize
f.Monoclonal Antibodies binds specifically to the CD20 antigen on B lymphocytes
g.Induces cell lysis through antibody-dependent cell-mediated cytotoxicity, complement-dependent
cytotoxicity, and apoptosis
h.May sensitize chemoresistant B-cell lines, possibly potentiating the effects of standard
chemotherapy
i.Pretreatment of lymphoma B-cell lines with rituximab before chemotherapy produces a synergistic
cytotoxic effect.
j.Pretreatment may sensitize cells to chemotherapy by downregulating the expression of
antiapoptotic factors IL-10 and bcl-2, which are highly expressed in B-CLL.
k.Because CD20 is a pan-B–cell antigen, rituximab has potential application in B-CLL
l.Assessed both alone for the management of patients with CD20+ B-CLL
HSP-90
D.Heat shock proteins (HSPs)
a.“Molecular chaperones’’ that protect cellular proteins from degradation
b.Responsible for the correct folding of a large number of proteins, which allows these proteins to
achieve their functional conformation
c.Regulate many signaling proteins involved in proliferation and carcinogenesis, such as Akt, HER2,
c-Met, androgen receptors, and Raf1

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