Abzyme

An abzyme (from antibody and enzyme), also called catmab (from catalytic monoclonal antibody), is a
monoclonal antibody with catalytic activity. Molecules which are modified to gain new catalytic activity
are called synzymes. Abzymes are usually artificial constructs, but are also found in normal humans (anti-
vasoactive intestinal peptide autoantibodies) and in patients with autoimmune diseases such as systemic
lupus erythematosus, where they can bind to and hydrolyze DNA. Abzymes are potential tools in
biotechnology, e.g., to perform specific actions on DNA.

PRINCIPLE:

• Lowering activation energy

• Stabilizing less favorable intermediates

NATURALLY OCCURING:

• 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 characterized 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 .

APPLICATIONS:

• Great potential in the pharmaceutical industries.

• Detoxification of cocaine.

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

• 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).
 • Inactivate viruses.

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

• In Israel Advanced Biotech is producing catalytic antibodies for the treatment of gram-negative
sepsis, targeting the endotoxin LPS.

• 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.

HIV treatment:

In a June 2008 issue of the journal Autoimmunity Reviews, researchers S Planque, Sudhir Paul, Ph.D, and
Yasuhiro Nishiyama, Ph.D of the University Of Texas Medical School at Houston announced that they
have engineered an abzyme that degrades the superantigenic region of the gp120 CD4 binding site. This
is the one part of the HIV virus outer coating that does not change, because it is the attachment point to T
lymphocytes, the key cell in cell-mediated immunity. Once infected by HIV, patients produce antibodies
to the more changeable parts of the viral coat. The antibodies are ineffective because of the virus' ability
to change their coats rapidly. Because this protein gp120 is necessary for the HIV virus to attach, it does
not change across different strains and is a point of vulnerability across the entire range of the HIV
variant population.

The abzyme does more than bind to the site, it actually destroys the site, rendering the HIV virus inert,
and then can attach to other viruses. A single abzyme can destroy thousands of HIV viruses. Human
clinical trials will be the next step in producing treatment and perhaps even preventative vaccines and
microbicide.