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Articles and Reports

Alternatives to Animal Research and Testing

Alternatives to Ascites Production of Monoclonal Antibodies
by John McArdle, Ph.D.
Alternatives Research and Development Foundation
Eden Prairie, Minnesota

Related Uses of Alternatives

Because in vivo production of monoclonal antibodies involves the largest number of animals and the greatest degree of suffering, it has received the most attention for the development of in vitro replacement alternatives. There are, however, three additional aspects of the process for which humane alternatives are appropriate and needed.
As mentioned above, the initial immunization procedures are most commonly done in vivo, although in vitro techniques are available in many cases. There is a need to further develop these in vitro options so they can be applied to the broad range of MAb needs, not just the production of human-specific antibodies.

Because of serious humane concerns related to its production, the use of fetal calf serum and similar products with in vitro alternatives (either for MAbs or in general) represents another candidate for development of appropriate replacements. Whenever possible, hybridoma cells should be conditioned to grow in serum-free media. This has the additional advantages of reducing the overall expense and post-production processing of the monoclonal antibodies. More than a decade of experience in Europe suggests this type of switch can be easily accomplished with little or no decrease in the production of MAbs. All of the high yield alternatives described above are designed to work effectively without the use of animal serum in their culture media.

Finally, there is a need in the production of hybridomas to replace the use of animal cells with those derived from humans. This is already a critical concern for MAbs produced for therapeutic applications, since murine-derived antibodies are severely limited for effective use in human recipients. For this reason, clinical uses of such antibodies focus on those derived from human cells. To completely replace the use of animals in all steps of MAb production, such concerns need to become more generalized among all producers and consumers of monoclonal antibodies.

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