MONOCLONA

L
ANTIBODIES
ANT IB ODI ES

PROTIENS SYNTHESIZED IN
BLOOD
IMMUNITY IN BLOOD
BLOOD SERUM
HETEROGENOUS
 WH AT ARE mA bs??
SPECIFIC LYMPHOCYTE
SINGLE TYPE Ab
SPECIFICITY AGAINST SPECIFIC
ANTIGEN
DIFFICULT IN MAINTAINING
CANCER CELLS
IMMUNOGLOBULINS
Contents:
Discovery
mAb therapy
Structure and function
Production
Types
mAb technology
mAb theory
Applications
♣DISCOVER
Y♣
TH E MAGI C BU LLET
PA UL EHR LICH
Hu man-Mo use Hyb rid
Ce lls

Georges
Köhler
César
Milste in
Niels Kaj
Jer ne
GREG WINTER
MONOCLONAL
ANTIBODY
THERAPY
one specific antigen
stimulating the patient's
immune system
e.g.radioimmunotherapy
STRUCTURE
AND
FUNCTIONS
OF
MAb...
IgG 150kDa
2 diff. chains
Light chain kappa
lambda
Papain Fab Fc
Tu mor c ells.. .
ErbB2 HER2 breast cancer

ANTIBODIES recognize foreign

ANTIGENS...

MAbs are used to raise specific

antibodies on such surfaces of
tumors!!
 PRODUCTION
HYBRIDOMA CELL
PRODUCTION

RECOMBINANT
HYBRIDOMA
CELL
PRODUCTION
RECOMBINANT
Ab PRODUCTION
Repertoire cloning/phage
display/yeast display
Virus/yeast used instead of MICE
Rapid cloning Ig gene segment
Abs having slightly diff. amino
acid sequences
Ab of desired specificity are
selected
Th e “ + ” p oints...

specificity of Ab to recognize Ag
stability
therapeutic efficacy
detection
•TYPES OF
mAbs•
 MURINE MAbs
Initially HYBRIDOMA technology was
used

PROBLEMS
1.Reduced stimulation of cytotoxity
2.Mild allergic reactions
3.anaphylactic shocks
 CHIMERIC MAbs
Murine variable region fused
onto human constant region
Kappa light chain+IgG1 heavy
chain=Antibodies 65% human
Increases serum half life
 HUMANIZED MAbs
Grafting murine hypervariable amino
acid domains into human antibodies
95% human origin
Humanized antibody<parent murine
MAb
Introducing MUTATIONS like chain-
shuffling, site-specific mutagenesis, E-coli
mutator strains and others...
 HUMAN MAbs
Transgenic mice
OR
 phage display libraries

Transferring human genes into murine genome.

The mouse is then vaccinated against the human
immunoglobulin

Phage display libraries transforms murine Abs in

vitro into fully human Abs.
MAb Technology...
CHINA
Dr. Ma Lan, Yunnan university
Piece of paper test
Yunda Monoclonal Technology
Company
AIDS, Hepatitis B, Hepatitis C,
Prostrate Cancer, venereal disease
and so on...
mAb
theory
Antigen=Foreign invaders
Antibody=Natural defenses
Monoclonal Antibodies
Protect
diagnose
Pure antibody prod.
Immortal cells
Tumor cell with mammalian
cell fusion
1 type of cell i.e. Hybridoma
hence monoclonal
Many kinds of cells-
polyclonal
 Cancer treatment
Bind only to cancer cells
Show immunological response
Modification
Bispecific antibody
ADEPT-antibody directed enzyme
prodrug therapy
ADCC-antibody dependent cell-mediated
cytotoxicity
And others...