1. Monoclonal Antibodies Large scale production and their implications in AIDS research

2. 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

3. 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).

4. 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”

5. Development of mAbs (in vivo) : fusing B cells from the immunized mouse with myeloma cells

6. 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.

7. 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

8. 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.

9. 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.

10. Future Directions Three human nmAbs have already undergone phase I testing. Prevention of mother-to-child transmission through breast milk.