EGFR
EGFR
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HealthValue
IgG1
IgG2
VL
CL
VH
CH1
CH2
CH3
THE
Fc
REGION
hinge
Immune
effector
cell
FcgR
cytotoxic
mediators
ADCC
Cancer cell
Cancer cell
polymerization of C9 drills
holes in target cells
Fc fragment
activates
complement
polymerization of C9 drills
holes in target cells
Fc fragment
activates
complement
There are 4 IgG subclasses, that have small differences in the amino acid sequences of the constant regions (CH1, CH2 & CH3) of the heavy chains : IgG1, IgG2, IgG3, IgG4.
IgG subclass
complement activation
Binding to Fc Receptor
1
2
3
4
++
+
+++
0
+++
low
+++
+
Anti EGF receptor antibodies can be of the IgG1 type ( cetuximab), or of the IgG2 type (panitumumab). There is no reason to link their clinical efficacies to the above general biological features of the subclasses, as many other factors are involved, such as activity on downstream phosphorylations in the EGFR controlled pathways.
ADCC antibody dependent cellular cytotoxicity
IgG1 (Cetuximab, Nimotuzumab, Matuzumab, Zalutumumab, Ipilimumab, IMC A12) & IgG2 (Panitumumab, **Tremelimumab, CP-751,871) : Biological activities on complement and ADCC*
Anti EGFR monoclonals can destroy cancer cells through many pathways, among which complement activation, and triggering of ADCC (antibody dependent cellular cytotoxicity) of immune effector cells, thanks to the activation of the Fc receptors on their membranes by the Fc regions of the monoclonals
MONOCLONALS
abatacept
abciximab
adalimumab
alefacept
alemtuzumab
anti KDR
basiliximab
belatacept
bevacizumab
CDP 791
cetuximab
dacluzimab
denosumab
eculizumab
efalizumab
etanercept
IMC 1121
infliximab
ipilimumab
lumiliximab
Mab 806
mapatumumab
matuzumab
natalizumab
nimotuzumab
ocrelizumab
ofatumumab
omalizumab
palivizumab
panitumumab
ranibizumab
rituximab
ticilimumab
trastuzumab
VEGF Trap
zalutumumab
ABOUT MONOCLONALS
what is a monoclonal
chains & fragments
therapeutic fields
what are CDs
types of monoclonals
fusion proteins
cells to build monoclonals
making monoclonals
IgG1/IgG2 differences
F(ab) fragments
Fc fragment
Fc structure
Fc e receptors
BioTherapies
antisense
cell therapy
exon skipping
gene therapy
hemopoietic prog.
monoclonals
protein kinases
recombinant prot.
stem cells
Pathways
Adams
AKT
amino acids
complement
cancer pathways
cdk
DPP IV
EGF
EGFRvIII
GPCR
G proteins
ILGF
kinome
Kras
mannose P
NFKB
nucleotides
protein kinases
proteins
Ras
RET
sheddases
sunitinib/sorafenib
VEGF
Wnt
Cells/organelles
cell cycle
cells
chromosomes
DNA repair
exons
hemopoietic prog.
introns
lysosomes
mb. receptors
membrane CDs
mitochondria
proteasomes
stem cells
DISEASES
bird flu
cancer
diabetes
human growth hormone diseases
lysosomal diseases
mitochondrial diseases
multiple sclerosis
myelodysplastic sd
myopathies
osteoporosis
paroxysmal nocturnal hemoglobinuria
psoriasis
*for antiEGFR monoclonals
**was Timilimumab
Table for anti EGFR monoclonals