APC
MHC
Ag
CD 80
CD 86
CD 86
CD 80
TCR
Abatacept / Belatacept
Abatacept / Belatacept
CO-ACTIVATION
INHIBITION
ACTIVATION
LYMPHOCYTE
HealthValue
All about monoclonals
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- ABATACEPT & BELATACEPT : the CTLA-4-Igs
Activation of T lymphocytes is due to their stimulation by presentation of the Ag (carried by the major histocompatibility complex MHC) to the TCR (T cell receptor), but also to a co-stimulation by APC (antigen presenting cell) membrane glycoproteins CD 80 and CD 86. Both act on the T lymphocyte :
- on the CD 28 receptor, which co-activates it
- on the CTLA-4 / CD152 (cytotoxic lymphocyte associated antigen), which inhibits this activation, but a bit later.
CD 28
CTLA-4, CD 152
CTLA-4-Igs are fusion proteins between the extra-cellular portion of the CTLA-4 receptor, and the Fc fragment of a human IgG : learn more about the Fc fragment
- Abatacept (aimed primarily at Rheumatoid Arthritis), respects the natural structure of CTLA-4.
- Belatacept (aimed essentially at transplantation), has enhanced activity thanks to 2 amino acid substitutions : a leucine by a glutamic acid, an alanine by a tyrosine.
Abatacept and Belatacept block CD 86 and CD 80, but Belatacept blocks them more powerfully, and is especially active in blocking the CD 86 / CD 28 interaction.
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IPILIMUMAB**
TREMELIMUMAB*
- IPILIMUMAB / MDX010 (IgG1) & TREMELIMUMAB (IgG2**), the fully human anti CTLA-4 monoclonals
Contrarywise to CTLA-4-Igs, essentially immunosuppressant, Ipilimumab & Ticilimumab, the fully human anti CTLA-4 monoclonals, block lymphocyte inhibition due to CTLA-4 , and thus enhance the anticancer immune defences. An ongoing trial associating Ipilimumab & GVAX immunotherapy (prostate cancer cell lines that have been modified to secrete GM-CSF) showed promising data at ASCO Prostate in February 2007.
CTLA-4 STRATEGIES
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
DISEASES
bird flu
cancer
diabetes
human growth hormone diseases
lysosomal diseases
mitochondrial diseases
multiple sclerosis
myelodysplastic sd
myopathies
osteoporosis
paroxysmal nocturnal hemoglobinuria
psoriasis
BioTherapies
antisense
cell therapy
exon skipping
gene therapy
hemopoietic prog.
monoclonals
protein kinases
recombinant prot.
stem cells
Cells/organelles
cell cycle
cells
chromosomes
DNA repair
exons
hemopoietic prog.
introns
lysosomes
mb. receptors
membrane CDs
mitochondria
proteasomes
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
see  page on Belimumab & Atacicept
*Tremelimumab was Ticilimumab
** Ipilimumab remarkable success in Metastatic late stage Melanoma
** Check IgG1, IgG2 differences