INTRODUCTION

AB ZYMES (Antibody + Enzymes)

 Monoclonal antibody
 Catalytic activity
 Artificial construct
 Normal humans
 Auto immune diseases
PRINCIPLE
 Lowering activation energy
 Stabilizing less favorable intermediates
ANTIBODIES
 FORMATION OF ABZYMES
Anti- idiotypic approach: from enzymes to
abzymes
MONOCLONAL ANTIBODIES
 NATURALLY OCCURING
ABZYMES
 Antibodies with catalytic activities were isolated from sera of patients with
different diseases. The first natural abzymes were obtained by means of
antibody purification from human serum.

 Antibodies with protease activity against vasoactif intestinal peptide (VIP)

were first isolated in the serum of patients with asthma.

 This VIP-ase activity was also shown to be present on proteins, that are
monoclonal human light chains found in urine of patients with
multiple myeloma.

 Other protease activities were charaterized for cleaving of throglobulin in

the serum of patients with Hashimoto thyroiditis, or for hydrolyzing factor
VIII in hemophilia patients infused with homologous factor VIII .

 DNA hydrolyzing autoantibodies were also isolated from the sera of patients
with systemic lupus erythematosus or rheumatoid arthritis .
 METALLO AND HEMOABZYME
 The idea to produce metalloenzymes or hemoenzymes was to generate antibodies
able to cleave stable chemical bonds or to catalyze peroxidase-like reactions.

 In 1989, an antibody catalyzing the hydrolysis of a Glycine-Phenylalanine bond was

obtained by using as the antigen an hapten that not only induce the selective
recognition of the Gly-Phe sequence, but also induce
the generation of residues able to complex a metal ion. When complexed with zinc,
this antibody exhibits a good catalytic activity.

 Hemoabzymes obtained are able to catalyze peroxidase-like activities and could be

very interesting tools for the enantioselective oxidation of molecules.
 APPLICATIONS OF
ABZYMES
1.Great potentialIndustrial applications
in the pharmaceutical industries.

2. Detoxification of cocaine.
3. Specific targeting of cancer cells unique determinants, called tumor cell antigens, on
their surface that are lacking in normal cells.

4. One application could concern the use of hydrolytic properties of abzymes to activate
prodrugs. By targeting this activity in the vicinity to tumor cells, prodrugs could be
transformed into cytotoxic compounds directly on tumor cells.
This anti-cancer therapy is designed as
Antibody-Directed Abzyme Prodrug Therapy (ADAPT)
5. Inactivate viruses.

6. High abzyme activity is observed in blood of pregnant women.

7. In Israel Advanced Biotech is producing catalytic antibodies for the treatment of

gram-negative sepsis, targeting the endotoxin LPS.

8. Finally, all researches aimed to produce antibodies with a sequence-specific protease

activity could open new ways for anti-virus therapy and for the conception of new
vaccines.