Thursday, June 10, 2010
A team of researchers has developed a method to produce cells that
kill tumour cells in the lab and prevent tumours forming in mouse
models of cancer. Although the current work is in cells and mouse,
if the research transfers to human biology, the new type of cell
could be a new source for cell-based anticancer therapies.
The cells were produced by knocking out a single gene essential in
the pathways of development of immune cells: the modified cells
become a novel type, which the authors call Induced T to Natural
Killer Cells (ITNK cells).
Many cell types cooperate in the immune system to battle invaders,
such as bacteria and viruses, and to remove abnormal or dead cells.
T lymphocytes/T cells play an important part in defending against
pathogens and abnormal self cells. They are thought also to play a
role in autoimmune disease.
In this research, T cells were transformed into cells similar to
another type, Natural Killer (NK) cells, which commonly act against
viruses and cancer cells.
"We have been examining ways to produce clinically useful immune
system cells," explains Peng Li, PhD student and first author on
the publication, from the Wellcome Trust Sanger Institute. "We had
shown that a gene called Bcl11b was essential for normal
development of immune system cells - and of particular interest in
the development of T cells.
"Here we can see the fruits of that work: we show, for the first
time, that we can modify the developmental fate of immune system
cells to produce a novel type that - if we can see the same effect
in humans - could be of enormous value in cancer treatment."
The Bcl11b protein is a master switch that works by regulating the
activity of other genes and it was known to be important in the
immune system. However, this role in T lymphocyte development is
entirely novel.
In the careful research, the team first showed that the Bcl11b gene
was active only in T cells in the immune system and that its
activity was needed at the earliest stages of production of T
cells. When the team knocked out the Bcl11b gene, the mice produced
no T cells.
"Remarkably, the mice lacking the Bcl11b gene produced a new type
of immune system cell - the Induced T to Natural Killer cells,"
explains Dr Pentao Liu, senior author on the project from the
Wellcome Trust Sanger Institute. "This is the first time we have
seen these cells and the first time a gene regulator like Bcl11b
has been shown to carry out such an important role in T
cells.
"Even more important, we can see that these reprogrammed killer
cells can attack cancer cells, whether in test tubes or in mouse
models."
The ITNK cells killed melanoma and lymphoma cells in experiment in
test tubes and were much more efficient than unmodified Natural
Killer cells in the mouse and in human.
But they worked also on cancers. When tumour cells were injected
into mice they produced at least tenfold fewer tumour foci in the
Bcl11b-deficient than in Bcl11b-competent mice.
"The reprogrammed killer cells were effective in preventing
metastasis - spread of the tumour in mice," explains Dr Francesco
Colucci, from the University of Cambridge School of Clinical
Medicine Dept of Obstetrics & Gynaecology. "The killing seems
to be specific to the tumour cells and the normal cells seem to be
spared.
"This is a really exciting development that could, if it can be
transferred to humans, lead to development of new effective
anticancer treatments. The results are stunning. One problem with
cellular therapies is that one needs to produce large number of
cells, something this work suggests could be done fairly easily
with reprogrammed killer cells"
The team also looked at the effects of the cells in the medium term
and showed that the ITNK cells continued to survive for at least
three months.
The team also looked at the effects of the cells in the medium term
and showed that the ITNK cells continued to survive for at least
three months. Equally important, they could find no evidence of
abnormality in the mice carrying ITNK cells. This suggests that
ITNK cells do not indiscriminately kill normal cells or cause other
damage, leading to optimism that ITNK cells might perform well in
future therapies.
###
Thanks to Wellcome Trust Sanger Institute for this article.