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Jun 15, 2008 (Vol. 28, No. 12)

Methods for Maximizing Antibody Yields

New Technologies Could Help Usher in Lower Costs and Increased Availability

  • Breaking Bottlenecks

    “Another aspect to consider is that when using CHO cells or other mammalian cell systems, current success depends on the particular proficiency of the organization using the system and the particular cell subline or strain of the original culture,” Dr. Cacciuttolo said.

    Since CHO cells have been in circulation for so long, there are many variants, some separated by thousands of generations. Clearly, the isolates described by Dr. Birch and his team at Lonza are light years away from many of the other CHO cell lines in circulation, and biotechnologists need to be aware of this. For both proprietary and biological reasons it is expected that newer cell lines are much more consistent.

    But even assuming consistent advances in antibody production at both the up- and downstream ends, recombinant antibodies will still be vastly more expensive to produce than small molecule therapeutics.

    Dr. Werner feels that this could create a stranglehold on the sector, clouding the possibility of commercial success. To avoid such a dismal outcome he recommended a number of promising alternatives to conventional antibody therapeutics that could dramatically lower costs.

    These include artificial scaffolds, protein backbones that hold the variable regions and are derived from a variety of naturally occurring protein families. They are noted for their simple structure and robust behavior and can be engineered to high affinity and specificity. Because they are smaller and less complex than complete, naturally occurring antibody molecules, they could be produced in microbial systems.

    Other modifications of the molecules that would extend their half-life or improve their effector functions can be engineered, providing an additional degree of performance with cost-lowering potential.

    Moreover, since the antibody-scaffold technology is quite recent, the IP situation is not nearly as crowded as that of recombinant antibodies.

    In this latter case, while none of these new antibody substitutes has seen clinical exposure, the next few years will test their value. “This therapeutic success will be crucial in gaining confidence in alternative immunotherapies,” Dr. Werner concluded.

  • K. John Morrow Jr., Ph.D., is president of Newport Biotech Consultants.

    Web: www.newportbiotech.com.

    E-mail: kjohnmorrowjr@insightbb.com.


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