T B cells

T cells
( T
Macrophages

Killer cells
(HLA)

2004 Myfortic
2001 Alemtuzumab* (Campath-1H)
1999 Sirolimus (Rapamune); Thymoglobulin
1998 Basiliximab (Simulect)
1997 Daclizumab (Zenapax); Rituximab* (Rituxan)
1995 Mycophenolate (CellCept); Neoral
1994 Tacrolimus (Prograf, FK 506)
1986 Muromonab-CD3 (OKT3)
1983 Cyclosporine (Sandimmune)
1981 Anti-thymocyte globulin (Atgam)
1963 Corticosteroid
1962 Azathioprine


Hydrocortisone 1

Prednisolone 10

Methylprednisolon 12
e
Dexamethasone 100

The Effects of
Glucocorticoid
The molecular
Mechanism of
Glucocorticoid
 NF-kB

I-kB Cytokines

Adhesion
molecules
Virus infection Growth
NF-kB factors
Ultraviolet light
Chemokines
TNF-

Interleukin-1
 NF-kB

I-kB Cytokines

Adhesion
molecules

NF-kB Growth
factors

Chemokines

-------


( DNA )

Cyclophosphamide Azathioprine
(Endoxan) (Imuran)


Cyclosporin (Sandimmune, )
 Immunosuppressant Certican 2008
Myfortic 2002
History
Anti-IL-2R 1997
Mycophenolate mofetil 1991
Neoral 1990
Tacrolimus 1987
OKT3 1981
Deoxyspergualin 1981
Leflunomide 1978
Rapamycin 1977
Cyclosporine 1976
Mizoribine 1975
Antilymphocyte serum 1967
Azathioprine 1963
Methotrexate 1961
6-MP 1959
Cyclophosphamide 1959
Cortisone 1949
 Cyclosporin (Neoral )

- 50ml/
- 100 25
Neoral Comparison of formulations

Cyclosporin
Sandimmun Neoral Gengraf
in water
 Cyclosporin

 Effects of Cyclosporine on
Glomerular Circulation in Rat1

Control Vasoconstricted arteriole (arrow) after

14 days of oral cyclosporine therapy

1. English et al. Transplantation 1987; 44: 135-141.

12-01 1.4
Tacrolimus (FK506, Prograf)
Absorption of tacrolimus at steady-state in kidney
transplant patients

35 Day 3
Tacrolimus concentration

Week 3
25 Month 3
(ng/mL)

15

5
0
0 2 4 6 8 10
12 Time after oral dosing (hours)
Undre NA et al. Transplant Proc 1998;30:1299302
 Rapamune
sirolimus 1mg/tab

* Trademark
Rapa Nui ( )
Dosage and Adminatration

Available in 250mg capsules

: 52 /
: B021757100
 Purine Synthesis Pathway

DNA GTP
synthesis Nucleic acids

De Novo
Pathway

inosine xanthine guanosine

PRPP
monophosphate monophosphate monophosphate

Salvage hypoxanthine xanthine guanine

Pathway
 Purine Synthesis

DE NOVO SALVAGE
PATHWAY PATHWAY
T- and B- Most
lymphocytes Neurones
cell
 MYCOPHENOLATE MOFETIL
MECHANISM

Mycophenolate in vivo
MPA
Mofetil hydrolysis GTP
Nucleic acids

De Novo
Pathway
IMPDH
inosine xanthine guanosine
PRPP
monophosphate monophosphate monophosphate

Salvage hypoxanthine xanthine guanine

Pathway
 Purine Synthesis

DE NOVO SALVAGE
PATHWAY PATHWAY
T- and B- Most
lymphocytes Neurones
cell

IMPDH

MYCOPHENOLATE
MOFETIL
 Clinic Safety Profile

Principal Adverse Reactions (%) summary at 1 Year

*All patient received cyclosporine and corticosteroids

 Immunosuppressant Mechanism
Anti CD3 mAb

Sirolemus

CellCept

CsA, Tarcolimus

Azathioprine (Imuran).
Cyclophasphomide (Endoxan).
Mycophenolate (CellCept).
Sirolimus (Rapamune)
Corticosteroid.
T
Calcineurin
Cyclosporine (Sandimmune).
Tarcolimus (Prograf).
T
Anti-Thymocyte Globulin ( T ).
OKT3 (Muromonab-CD3)( T TCR).
Daclizumab (Zenapax), Basilixmab (Simulect)( IL-2
).
Therapeutic Monoclonal
Antibodies
Antibody
Structure

www.cartage.org.lb/en/themes/sciences/lifescience/GeneralBiology/Physiology/Lymphatic
System/Antibodymediated/ANTIBODY.gif

Fuse cells and plate
in selected media
Myeloma
cell culture
Screen hybrids for
synthesis of desired
antibody

HGPRT-Ig-
myeloma cells
Selected
hybridoma
Mass
culture
growth

HGPRT+lg+ MoAb
B cells

B Cell

/

Immunization

Adapted from Khler et al. Nature. 1975;256:495.

Conjugated monoclonal antibodies
Radiolabeled MAbs: attached with
radioactive particles.

Chemolabeled MAbs: attached with

chemotherapy drugs.

Immunotoxins MAbs: attached with toxins.

From the American Cancer Society



CDR: complementarity-determining regions ( )

 Omalizumab Xolair
(rhuMAb-E25)
)

Tanox


Anti-IgE


10

Omalizumab
 IgE

IgE

: :
(Mast-cell antihistamines, steroids
stabilization): antileukotrienes
cromones,
isoprenaline

Adapted from Roitt J. Essential Immunology 1994

anti-IgE IgE
 anti-IgE :