Biomedical Engineering Reference
In-Depth Information
The immunopotentative effects of IL-2 rendered it an obvious target for clinical application. At
the simplest level, it was hoped that administration of exogenous IL-2 could enhance the immune
response to a number of clinical conditions, including:
cancers,
T-cell and other forms of immunodefi ciency,
infectious diseases.
9.2.1 Interleukin-2 production
As was the case for most other cytokines, medical appraisal/use of IL-2 was initially impracti-
cal due to the minute quantities in which it is normally produced. Some transformed cell lines,
most notably the Jurkat leukaemia cell line, produces IL-2 in increased quantities, and much of
the IL-2 used for initial characterization studies was obtained from this source. Large-scale IL-2
production was made possible by recombinant DNA technologies. Although the IL-2 gene/cDNA
has now been expressed in a wide variety of host systems, it was initially expressed in E. coli , and
most products being clinically evaluated are obtained from that source. As mentioned previously,
the absence of glycosylation on the recombinant product does not alter its biological activity.
Proleukin is the tradename given to the recombinant IL-2 preparation manufactured by Chiron
and approved for the treatment of certain cancers. It is produced in engineered E. coli and differs
from native human IL-2 in that it is non-glycosylated, lacks an N-terminal alanine residue, and
cysteine 125 has been replaced by a serine residue. After extraction and chromatographic purifi -
cation, the product is formulated in a phosphate buffer containing mannitol and low levels of the
detergent SDS. The product displays typical IL-2 biological activities, including enhancement of
lymphocyte mitogenesis and cytotoxicity, induction of LAK/NK cell activity and the induction of
IFN-γ production.
9.2.2 Interleukin-2 and cancer treatment
The immunostimulatory activity of IL-2 has proven benefi cial in the treatment of some cancer
types. An effective anti-cancer agent would prove not only medically valuable, but also commer-
cially very successful. In the developed world, an average of one-in-six deaths is caused by cancer.
In the USA alone, the annual death toll from cancer stands in the region of half a million people.
There exists direct evidence that the immune system mounts an immune response against most
cancer types. Virtually all transformed cells express (a) novel surface antigens not expressed by
normal cells or (b) express, at greatly elevated levels, certain antigens present normally on the cell
at extremely low levels. These 'normal' expression levels may be so low that they have gone un-
noticed by immune surveillance (and thus have not induced immunological tolerance).
The appearance of any such cancer-associated antigen should thus be capable of inducing an
immune response, which, if successful, should eradicate the transformed cells. The exact elements
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