Clinical Biochemistry

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Chapter III

Part 2

Engineered Pharmaceuticals in
Medicine and Industry
Synthesis of Pharmaceuticals from Genes Cloned in
Eukaryotes
Some of the human proteins that have been synthesized from genes cloned in eukaryotic cells.

Human protein Host Vector

Insulin Mouse cells Integrated plasmid

Somatostatin Monkey cells SV40

HGH (Somatotropin) Mouse cells Papilloma virus

Parathyroid Rat cells Retrovirus

Gonadotropin Monkey cells SV40

Interferons Yeast and Mouse 2μm plasmid

Interleukins Insect cells Baculovirus

Factor VIII Hamster cells Integrated plasmid


A- Production of recombinant Vaccines

• Vaccines are antigens:


• They are the inactive forms of the viruses that stimulate the
immune system to produce antibodies in order to protect the
body from subsequent attacks.
• The advantages of producing recombinant
Vaccines:
• 1- To avoid any active virus that may cause the disease and
insure 100% inactivation.
• 2- Some viruses are not growing in tissue culture such as
Hepatitis B.
There are methods for the production of
recombinant vaccines:-
• I- cloning in expression vectors
• II- Using harmless living virus (Vaccinia virus)
• III- Production of recombinant protein
• I- Cloning of vaccines in expression vectors:
• by inserting a gene coding for the antigenic
protein of the virus into an expression vector.
• e.g. Hepatitis B, malaria viruses in yeast cells,
banana vaccine within banana cells and also
foot-and mouth in cattle’s disease).
Examples of Recombinant Vaccines against human and animal
pathogens
Hepatitis B virus vaccine: Hepatitis B surface antigen (HBsAg) from patient’s
blood is inserted into yeast expression vector.
II- Using Recombinant Vaccinia Viruses:
(a harmless living virus for smallpox)
III- Production of Recombinant sCD4 protein may fight AIDS:
Blocking HIV infection of cells in culture, using a soluble CD4.
Recombinant HIV proteins (antigens) may be used as immunogenes for the
production of AIDS vaccines.
B- Production of Antibodies
Production of Genetically Engineered Drugs for Tissue
Transplantation
• Zenapax (FDA approved drug)
• Zenapax is a monoclonal antibody genetically engineered in mice but 90%
of its amino acids are human amino acids to avoid allergy.
• It prevents rejection of transplanted organs without the side effects of the
commonly used immune system suppression agents.
• It is used for liver, kidney, lung and heart transplantation.

• It doesn't shut down the whole immune system but only inactivates the
WBCs that attack the new organ and doesn’t affect the healthy cells.
• B-lymphocytes bind to cell surface antigen from transplanted cells and
produce cytokine protein (Interleukin 2 or IL 2) that bind to receptors on
T-lymphocytes. The activated T-cells stimulate proliferation and
production of antibodies from B-cells against the transplanted tissues.
• Zenapax works by binding to receptors for IL 2 protein on the surface of
the activated cells only and does not affect the other cells in the immune
system.

• Zenapax showed less kidney rejection (22% of the patients) than the most
commonly used immunosuppressant drug Cyclosporine (35% of patients).
Tissue Transplantation
• Allotransplantation Xenotransplantation

• Transplanting organs Transplanting organs


in the same species from one species to
another.
• (Human to human)
(Animals to Human)
E.g. heart valves from
pigs to human

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