Monoclonal Antibody

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 Papain

Fab

lambda 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 chainshuffling, 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 cellspolyclonal

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...