Can our immune cells be summoned to fight cancer by
stimulating them from within their nucleus? Netherlands Cancer
Fred van Leeuwen and
Heinz Jacobs have received a 675.000
Euro TOP grant to investigate whether this strategy can improve
current immunotherapy outcomes.
has been very successful in some cancer patients, but not in
others. This emerging treatment option stimulates the patients' own
immune cells to fight cancer cells. One of the possible strategies
to improve the treatment outcome is to stimulate immune cells not
just from the outside - as current immunotherapies do - but from
within their nucleus as well.
Fred van Leeuwen and
Heinz Jacobs and their research groups at the Netherlands
Cancer Institute join forces to investigate this. They have
TOP grant of 675.000 Euro (5 years) from ZonMw, the Netherlands
Organization for Health Research and Development.
Multiply and attack
One needs to dive deep into the human cell to understand why Van
Leeuwen and Jacobs explore this topic. A journey into the core of
the cell: the nucleus, containing DNA. Cells wrap their DNA around
proteins to form a compact package that fits into their nucleus.
Another type of protein can make small, so-called epigenetic
changes to the DNA package to activate or silence part of the
genetic code, changing the behavior of the cell.
Immune cells called T-cells change their behavior multiple times
during their lifespan. "They wait until they bump into something
foreign like a bacteria or a tumor, upon which they become active,
multiply and attack", Van Leeuwen explains. "We have discovered
that immune cells lacking a protein called DOT1L look like they've
already been activated without having bumped into something
foreign. Apparently, this DOT1L epigenetic factor causes T-cells to
change their appearance."
Their TOP grant allows Van Leeuwen and Jacobs to determine
whether these seemingly activated immune cells can actually help in
combatting cancer. They'll try to unravel how the absence of DOT1L
causes immune cells to change their appearance, and how these cells
actually behave. Do they act according to their looks? Can they
fight cancer cells?
"Interestingly, a drug that inhibits DOT1L is already being
tested in a phase 1 clinical trial for patients with a specific
form of leukemia", says Van Leeuwen. "These patients have a gene
defect that causes DOT1L to be hyperactive. Once we understand how
the DOT1L protein influences the behavior of immune cells, this
inhibitor could possibly be used to push them towards fighting
About TOP grants
ZonMw TOP grants offer strong research groups the opportunity to
engage in new, risky lines of research. The grants are intended to
give them the opportunity to innovate in their research lines, in
terms both of content and of collaboration. More information about