Imagine that you’ve got advanced cancer, all the conventional treatments have
been exhausted and your life expectancy is dwindling. Then a doctor explains
to you that, in the lab around the corner, he’s been developing a new type
of treatment, maybe something so innovative that it hasn’t even been tried
on animals. You know your time may be limited, you know that others might
benefit from your bravery, but might just make things much worse. Do you
agree to it?
Cancer patients at the new Experimental Cancer Medicine Centre, at historic
Bart’s Hospital in London, are doing exactly that. With their doctors they
are fast-tracking development of drugs that would normally take more than a
decade to go from test tube to patient.
At the centre, which will be formally launched next month, doctors are
pioneering an approach called translational research. Supported by Cancer
Research UK, it’s different from conventional clinical trials, where a new
treatments is developed in the lab, tested on animals and then assessed for
safety and effectiveness on human beings according to a long and rigid
formula. Translational research is already common in the US and bypasses
this process by continually examining the effect of test treatments on
individual patients’ cells.
Bart’s is part of an initiative jointly funded by the Department of Health and
Cancer Research UK to set up a network of 17 experimental cancer centres in
Britain. The work at Bart’s will focus on a constant interplay between
scientists and patients. In translational research, if a treatment is having
a positive effect on a patient, the scientist can examine exactly why it’s
working and perfect it further. If it works on some patients and not others,
scientists can examine what molecular mechanisms are making the difference
and use that knowledge to refine and track the effect. If it’s not working
on anyone, they can close off blind alleys quickly.
The new centre will be led by John Gribben, a sociable Scot with a
let’s-get-things-moving attitude. He is the professor of experimental cancer
medicine at Bart’s. He will head the new unit with Professor Nick Lemoine,
the director of the Institute of Cancer at Bart’s and the London Queen
Mary’s School of Medicine and Dentistry. Professor Gribben, one of the few
translational cancer researchers in the country, divides his time between
patients and pipettes. He says the problem with traditional research is that
scientists in the lab tend to speak one language; doctors on the ward speak
another. Someone needs to be able to take laboratory findings and apply them
to people, and someone needs to take the clinical experiences of patients
back to the lab. “You need people with a foot in both camps,” he says. For
Professor Gribben, this close collaboration between ward and lab is
physically manifested in the brisk five-minute walk that links the cancer
unit at Bart’s and the science block at the medical school.
He often works with people with advanced cancers, which has advantages with
fast-tracking research. Although all potential fast-track treatments will
have undergone basic safety tests in the labs, such innovative treatments
will carry risks that people who have longer life expectancies might not be
prepared to take. All this has to happen with a rigorously enforced and
stringent consent procedure, of course. When Professor Gribben and his team
think they have a patient who might benefit from, say, a new drug that
targets cancer cells, they explain the potential risks and benefits. If the
patient agrees, the doctors constantly take blood or tissue samples to
monitor the therapy’s effect.
Professor Gribben came to Bart’s in 2005, specifically to develop
translational research, having spent nearly 20 years at Harvard University,
where patient care and research are more closely linked than in the UK. He
worked alongside the researchers who developed Glivec, the first of a new
breed of cancer drugs, which targets the specific molecular abnormality that
drives malignant growth. The breakthrough happened, he says, only because
researchers worked so closely with patients on a day-to-day basis.
“I find it hugely impressive that people should agree to take part,” says
Professor Gribben. “You get very motivated to do something, when you’re
working with the patients who are directly affected by cancer. You have to
recognise that for people like Lesley-Anne [see panel, facing page],
conventional treatments have failed and there’s a need to move faster.”
“That was the worst time. I thought I was going to die. Then Professor Gribben offered me a lifeline”
When Professor John Gribben looks at Lesley-Anne Robins today, he knows that,
were it not for the experimental treatments she has received, the
47-year-old mother of two from Bedfordshire would have died many years ago.
Robins had nonHodgkin’s lymphoma, a cancer of the white blood cells. She was
one of the first people in the world to receive a “mini-transplant” of
donated bone-marrow cells. The therapy employs the natural tendency of
implanted cells to attack the cells of their host, to fight the cancer.
Robins had already had conventional, aggressive treatment for lymphoma using
high doses of chemotherapy to blast the cancerous blood cells, and then
received transplants of new blood marrow cells to replace the ravaged
marrow. This aggressive treatment, which Robins had at Bart’s in 2000, is so
gruelling that Robins nearly died. But she felt well for four years after
it. Then in 2005 her cancer returned – and conventional treatment was out of
the question.
“That was my worst moment,” says Robins. “I thought, that’s it, I’m going to
die.” Professor Gribben, however, offered a lifeline – an experimental
mini-transplant, where patients are given much lower doses of chemo, and a
transplant not of their own bone-marrow cells, but of donated bone-marrow
cells.
His earlier research had indicated that donated cells, as opposed to the
host’s own cells, could actually fight the cancer.
“When I was offered the treatment, I knew I didn’t have a choice,” she says.
“My cancer was now incurable – at least, that’s what I thought. But
Professor Gribben explained to me the potential for the new treatment to be
a cure, even though I was only one of 24 patients ever to have had a
treatment like it. He put me at ease, and gave me confidence that this might
help.”
The treatment took place in March 2006 and this time the most gruelling part
was not the chemo but the weeks of isolation that followed it, to prevent
infection. Continuing tests revealed that the disease was on the wane, and
Professor Gribben added more donor marrow injections and an antibody
treatment called Rituximab as additional treatments. On its own, Rituximab
had not helped her, but now it helped to moderate the effect of donor marrow
cells so that they fought cancer, not normal cells.
A year and a half later, Robins feels great, and Professor Gribben is hopeful
that she’s cured. “I’d never before had the option of a cure, just of
controlling the disease,” she says. “Now I just want to enjoy life, and be
with my two daughters as much as possible.”
Beating cancer with transplants
For 15 years, Professor Gribben has been investigating the potential of cells
transplanted from other people to fight cancer. Working with blood cancers
such as leukaemia and lymphoma, he realised that bone-marrow cells
transplanted from donors did far more than replacing damaged marrow in the
patient.
“They actually seem to detect cancer cells in the recipient,” he says. It’s
all to do with process we know as rejection – when the white blood cells of
a host start attacking any transplanted organ or tissue. Likewise, if you transplant
white blood cells, or the bone marrow that creates them, into a patient, the
transplanted cells can start attacking the tissues of the patient.
But Professor Gribben discovered that some of these white cells home in on the
proteins on the outside of cells that mark them as cancer cells, rather than
proteins that mark them as “foreign” cells belonging to the host. This is
why Lesley-Anne Robins’ transplant seems to have had a curative effect. But
it is tricky balancing the potentially curative effect of donated white
cells, against their hostile effect on cells generally.
It is work with people such as Robins that has allowed Professor Gribben to
observe this effect. “I’ve taken her cancer cells, and shown in the
laboratory that they can be killed by cells in donor marrow. This was one of
the first demonstrations that these cancer-killing cells exist.”
Since Professor Gribben believes that the donor white blood cells are homing
in on a particular pattern of proteins on the surface of cancer cells he is
working on isolating the white blood cells that have this beneficial effect.
He wants to use them as the basis of a new cancer treatment. The next step
will be a much more refined version of the mini-transplant – and it might
form the basis of new treatments for all kinds of cancers, not just
lymphoma.
