Monoclonal Antibodies

Large scale production and their implications in AIDS research

What is an Antibody (Ab)?

• Protein (immunoglobulin)• Produced in plasma cells• Expressed by B-

lymphocytes (WBCs) • MW = ~150 kDa• 5 classes: • 2 heavy chains & 2 light

chains• Constant region &

variable region

Monoclonal Antibodies (mAbs)

• Homogeneous preparation of antibody molecules, produced by a single clone of B lineage cells, often a hybridoma, all of which have the same antigentic specificity.

• A hybridoma is a clone of hybrid cells formed by fusion with myeloma cells.

• Used in biomedical research, in diagnosis of diseases, and in treatment of diseases (i.e. viruses, infections and cancer).

Nobel Prize: 1984

• Dr. César Milstein (1927-2002), Dr. Georges Köhler (1946-1995) and Dr. Niels Jerne (1911-1994)

• “for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies”

Development of mAbs (in vivo):

fusing B cells from the immunized mouse with myeloma cells

In Vitro Production

• Tissue Culture.• 90% success rate and reduced costs.• 25,000 mAb are listed in Linscott’s Directory

(1998-1999).• Commercial interests: 0.1–10 g as small,

10–100 g as medium, and over 100 g as large.

• Three major uses: diagnosis, therapy, and research on and development of new therapeutic agents.

Taconic Monoclonal Antibodies

• Albany, NY• STAT-IV INTEGRA

Program: hollow-fiber bioreactors and roller bottle systems

• 2 chambers:– Contain cells and nutrient

medium

• Runs for 42 days• Produces up to 200 mg

of Ab per cycle• $1155/42 day cycle

Monoclonal Antibodies and AIDS

• Ferrantelli and Ruprecht (2002): Neutralizing antibodies against HIV – back in the major leagues?

• successes for neutralizing antibodies against HIV.• human monoclonal antibodies targeting conserved HIV

envelope epitopes potently neutralized primary virus isolates.

• successful passive immunization with human neutralizing monoclonal antibodies has emphasized the importance of neutralizing antibodies in controlling HIV infection and provided targets for developing antibody-response-based AIDS vaccines.

The role of nmAbs in AIDS

Time courses of viremia, CD4+ T cell counts, and CTL and nAb responses during HIV infection and disease progression.

Future Directions

• Three human nmAbs have already undergone phase I testing.

• Prevention of mother-to-child transmission through breast milk.