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Hybridomas, Genetic Engineering of 443

potential human consequences of the presence of these reagents. Therefore, it is certain that the requirements for
contaminants in therapeutic products, most regulatory large-scale production of hybridomas will increase. There
authorities have demanded the use of serum-free is a need to ensure that the conditions of culture are com-
processes for the production of therapeutic products patible with full and appropriate human glycosylation pro-
when available. filesofthesynthesizedimmunoglobulins.Therefore,work
to understand fully those conditions that allow this to take
A. Serum-Free Media place will continue.

Given the disadvantages described above, the growth of
cells in bioreactors using serum-free media offers an SEE ALSO THE FOLLOWING ARTICLES
alternative solution:
GENE EXPRESSION, REGULATION OF • IMMUNOLOGY—
Serum-free media reduce the risk of exposure to agents

AUTOIMMUNITY • MAMMALIAN CELL CULTURE •
of zoonotic diseases, like BSE, by being devoid of METABOLIC ENGINEERING • NUCLEIC ACID SYNTHESIS
animal-derived components. • PROTEIN FOLDING • PROTEIN STRUCTURE • PROTEIN
Serum-free media can be formulated with a low SYNTHESIS • TISSUE ENGINEERING • TRANSLATION OF

protein content to offer enhanced purity and higher RNA TO PROTEIN
quality of the final cultured product.
Historically, serum-free media have exhibited poor growth BIBLIOGRAPHY
characteristics compared to serum-supplemented media,
and for this reason have not been widely used as a replace- Borrebaeck, C. A. K., and Hagen, I. (eds.) (1993). “Electromanipulation
ment to serum-supplemented media. However, serum-free in Hybridoma Technology: A Laboratory Manual,” Stockton Press &
media technology is continuously improving and serum- W. H. Freeman/OUP, New York.
Butler, M. (1996). “BASICS: Mammalian Cell Culture and Technology,”
free media products have been shown to exhibit growth
Oxford University Press, Oxford.
and productivity characteristics that are comparable or su- Cambrosio, A., and Keating, P. (1996). “Exquisite Specificity: The Mon-
perior to serum-supplemented media. oclonal Antibody Revolution,” Oxford University Press, Oxford.
Delves, P. J. (ed.) (1994). “Cellular Immunology Labfax,” Academic
Press, London.
XXIII. CONCLUSIONS Malik, V. S., and Lillehoj, E. P. (eds.) (1994). “Antibody Techniques,”
Academic Press, London.
Mather, J., and Barnes, D. (eds.) (1998). “Animal Cell Culture Methods,”
The ability to produce monoclonal antibodies from hy-
Academic Press, London.
bridomas emerged from a technology developed in the Mizrahi, A. (ed.) (1989). Adv. in Biotechnological Processes Vol. 11,
early 1970s and reported in 1975. Since then monoclonal “Monoclonal Antibodies: Production and Application,” A. R. Liss,
antibodies have found wide application in research and in New York.
diagnostic tests because of their high specificity in recog- Seaver, S. S. (ed.) (1986). “Commercial Production of Monoclonal An-
tibodies,” Marcel Dekker, New York.
nizing antigens. However, the therapeutic application of
Springer, T. A. (ed.) (1985). “Hybridoma Technology in the Bioscience
monoclonal antibodies has taken a long time because of a and Medicine,” Plenum Press, New York.
range of side-effects associated with undesirable immune Wang, H. Y., and Imanaka (eds.) (1999). “Antibody Expression and En-
responses in humans of murine-derived antibodies. The gineering,” Oxford University Press, Oxford.
situation is now rapidly changing with the ability to pro- Harbour, C. and Fletcher, A. (1991). “Hybridomas: production and se-
lection,” In “Mammalian Cell Biotechnology: A Practical Approach”
duce humanized or fully human antibodies. This has en-
(M. Butler ed.), pp. 109–138, Oxford University Press, Oxford.
abled the approval of monoclonal antibodies for a range of James, K. (1990). “Therapeutic monoclonal antibodies—their produc-
therapies including transplantation, cancer, infectious dis- tion and application,” In “Animal Cell Biotechnology,” (R. E. Spier
ease, cardiovascular disease, and inflammation. There are and J. B. Griffiths, eds.), Vol. 4, p. 205, Academic Press, London.
presently eight antibodies approved by the FDA for thera- McCullough, K., and Spier, R. E. (1990). “Monoclonal antibodies in
biotechnology: Theoretical and practical aspects,” In “Cambridge
peutic use (see Table III) with several hundred awaiting the
Studies in Biotechnology,” Vol. 8, Cambridge University Press,
results of clinical trial. Because these approved antibodies Cambridge.
are human (or humanized) immunoglobulins they enable Fukuta, K., Abe, R., Yokomatsu, T., Kono, N., Nagatomi, Y., Asanagi,
effector functions to direct complement-dependent cyto- M., Shimazaki, Y., and Makino, T. (2000). “Comparative study of
toxicity to a target cell. Other biological effects are also the N-glycans of human monoclonal immunoglobulins M produced
by hybridoma and parental cells,” Arch. Biochem. Biophys. 378,
possible by conjugation of compounds to the antibody.
142–150.
Therapeutic antibodies are required in much larger Hiatt, A., Cafferkey, R., and Bowdish, K. (1989). “Production of anti-
quantities than those used in diagnosis or as laboratory bodies in transgenic plants.”