Biomedical Engineering Reference
In-Depth Information
Experiments conducted in the early 1980s showed that lymphocytes incubated
in vitro
with
IL-2 could subsequently kill a range of cultured cancer cell lines, including melanoma and colon
cancer cells. These latter cancers do not respond well to conventional therapies. Subsequent inves-
tigations showed that cancer cell destruction was mediated by IL-2-stimulated NK cells (i.e. LAK
cells). Similar responses were seen in animal models upon administration of LAK cells activated
in vitro
using IL-2.
Clinical studies have shown this approach to be effective in humans. LAK cells originally
purifi ed from a patient's own blood, activated
in vitro
using IL-2 and reintroduced into the patient
along with more IL-2, promoted complete tumour regression in 10 per cent of patients suffering
from melanoma or renal cancer. Partial regression was observed in a further 10-25 per cent of
such patients. Administration of high doses of IL-2 alone could induce similar responses, but
signifi cant side effects were noted (discussed later).
IL-2-stimulated cytotoxic T cells appear even more effi cacious than LAK cells in promoting
tumour regression. The approach adopted here entails removal of a tumour biopsy, followed by
isolation of T-lymphocytes present within the tumour. These tumour-infi ltrating lymphocytes
(TILs) are cytotoxic T-lymphocytes that apparently display a cell surface receptor which specifi -
cally binds the tumour antigen in question. They are thus tumour-specifi c cells. Further activation
of these TILs by
in vitro
culturing in the presence of IL-2, followed by reintroduction into the
patient along with IL-2, promoted partial/full tumour regression in well over 50 per cent of treated
patients.
Further studies have shown additional cancer types, most notably ovarian and bladder cancer,
non-Hodgkin's lymphoma and acute myeloid leukaemia, to be at least partially responsive to
IL-2 treatment. However, a persistent feature of clinical investigations assessing IL-2 effects on
various cancer types is variability of response. Several trials have yielded confl icting results, and
no reliable predictor of clinical response is available.
9.2.3 Interleukin-2 and infectious diseases
Although antibiotics have rendered possible the medical control of various infectious agents
(mainly bacterial), numerous pathogens remain for which no effective treatment exists. Most of
these pathogens are non-bacterial (e.g. viral, fungal and parasitic, including protozoal). In addi-
tion, the overuse/abuse of antibiotics has hastened the development of antibiotic-resistant 'super
bacteria', which have become a serious medical problem.
The most diffi cult microbial pathogens to treat are often those that replicate within host cells
(e.g. viruses and some parasites). For example, during the complex life cycle of the malaria proto-
zoan in humans, the parasite can infect (and destroy) liver cells and erythrocytes. Over 2 million
people die each year from malaria, with at least 200-300 million people being infected at any
given time. Some such agents have even evolved to survive and replicate within macrophages
subsequent to uptake via phagocytosis. This is often achieved on the basis that the phagocytosed
microbe is somehow capable of preventing fusion of the phagocytosed vesicle with lysozomes.
Examples of pathogens capable of survival within macrophages include:
•
Mycobacteria (e.g.
M. tuberculosis
, the causative agent of tuberculosis, and
M. leprae
, which
causes leprosy).
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