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PERSPECTIVES
154
www.nature.com/reviews/immunol
2004 Nature Publishing Group
PERSPECTIVES
Spleen cells (HGPRT+)
(Antibody producing)
Unfused
spleen
cells
Fused
spleen
cells
Hybridoma
Unfused
myeloma
cells
Fused
myeloma
cells
Cell death
Cell death
Proliferation
Figure 3 | Cell fusion and monoclonal antibody production. A schematic representation of hydridoma
technology. Spleen cells from an immunized mice are fused, using polyethylene glycol, with myeloma cells
that were rendered drug sensitive by a mutation in a growth essential gene HGPRT. The cell mixture is
then cultured in a medium containing the selective drug. As immune cells, although not sensitive to
HGPRT, survive for only about one week in culture and the myeloma cells are drug sensitive they will all die
within a week or so. The only cells that can survive are those hybrid myeloma cells that obtained a normal
HGPRT gene from the immune cells. These hybridomas can grow continuously in vitro and some secrete
antibody. By using appropriate screening technology, clones of cells that secrete antibody of interest can
be identified and expanded in vitro or in vivo to obtain large quantities of monoclonal antibody that can
subsequently be purified to homogeneity. HGPRT, hypoxanthine-guanine-phosphoribosyltransferase.
Modified, with permission, from REF. 19 Johns Hopkins University (2003). www.hopkins-arthritis.org.
PERSPECTIVES
antibody (Abbott Humira, adalimumab)
entered the market, which should be good
news for individuals with rheumatoid arthritis.
When Khler died in 1995, the monoclonal
antibody market was worth a few million US
dollars; in 2002 the monoclonal antibody
market was valued at four billon US dollars17.
Wood Mackenzies forecast for 2005 is nearly
nine billon US dollars. Monoclonal antibodymediated therapy now covers the fields of
cancer, infectious diseases, transplantation,
allergy, asthma and some autoimmune
diseases. The major therapeutic advantages of
monoclonal antibodies are their high specificity, the high affinity with which they bind to
targets and the limited side effects associated
with their use.
The beauty of science is in its unpredictability. The wondering scientist needs to
be protected, to be supported by institutions
such as the Basel Institute for Immunology
and the MRC; there, he/she can learn how to
be open minded, to be critical of data and to
question paradigms. Also, as Jerne told me, it
is important to avoid doing experiments
before understanding the meaning of the last
experiment. The late Steinberg used to tell
me, You are better off by publishing few
articles; at least you are saving some trees
(paper) and other peoples time. I believe it
was the freedom and multicultural atmosphere at the Basel Institute for Immunology
and the MRC that fostered collaboration
between scientists that shaped this major
156
Acknowledgements
I am grateful to F. Cochran and C. Akdis for critical reading of the
manuscript.
Online links
FURTHER INFORMATION
The Nobel Prize in Physiology or Medicine 1984:
http://www.nobel.se/medicine/laureates/1984/
Csar Milstein autobiography:
http://www.nobel.se/medicine/laureates/1984/milsteinautobio.html
Niels K. Jerne autobiography:
http://www.nobel.se/medicine/laureates/1984/jerneautobio.html
Georges J.F. Khler CV:
http://www.nobel.se/medicine/laureates/1984/kohler-cv.html
FURTHER READING
Brekke, O. H. & Sandlie, I. Therapeutic antibodies for human
diseases at the dawn of the twenty-first century. Nature Rev.
Drug Discovery 2, 5262 (2003)
Access to this interactive links box is free online.
www.nature.com/reviews/immunol
2004 Nature Publishing Group