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TRANSPLANTS of specially grown immune cells that home in on tumour cells
could help cure leukaemia, and possibly a wide variety of other cancers,
too.

In people with leukaemia, the bone marrow鈥攖he tissue that gives rise to
blood and immune cells鈥攂ecomes cancerous. The usual treatment is to
destroy the cancerous tissue and replace it with matched marrow to avoid any
chance of immune rejection. But almost 20 years ago, oncologists made the
surprising discovery that patients were much less likely to suffer a relapse if
the transplant was less than a perfect match.

The reason is that some of the immune system鈥檚 T cells are often transplanted
along with the bone marrow. If there鈥檚 a slight mismatch between donor and
recipient cells in surface proteins called minor histocompatibility antigens, or
MiHAs, these T cells track down and destroy any remaining cancer cells.

This 鈥済raft-versus-leukaemia鈥� response is so effective that researchers have
been eager to extend its use against leukaemia, and to see if it will work for
solid tumours as well.

But there is a big problem. In some cases, the donor immune cells will attack
healthy tissue as well as cancer cells鈥攁nd this graft-versus-host disease
can be fatal.

If doctors knew which MiHAs trigger the anti-cancer response, they could
deliberately trigger this response without causing graft-versus-host disease,
says Claude Perreault of the University of Montreal in Canada.

Out of the hundreds of MiHAs that can differ between donors and patients,
Perreault and his team decided to focus on one in mice known as B6^dom1. And
they struck lucky. When they gave mice with leukaemia a bone marrow transplant
plus specially grown T cells that target B6^dom1, 60 per cent of the animals
survived at least 100 days. Most strikingly, none of the animals that died
succumbed to graft-versus-host disease, even though B6^dom1 appears on every
cell the mouse鈥檚 body. That鈥檚 important, says Perreault, because if there are no
side effects, people could be treated repeatedly until the cancer goes into
remission.

Perreault believes that the key to the therapy鈥檚 success is that B6^dom1 is
more abundant on immune cells than other tissues. Finding similar MiHAs in
humans should not be too difficult, he adds.

If all goes well, Perreault says the technique could be in clinical trials in
as little as two years. 鈥淭his is extremely important work,鈥� says Francesco
Dazzi, a haematologist at the Imperial College School of Medicine at Hammersmith
Hospital in London.

He says the vast array of human MiHAs has always made controlling
graft-versus-host rejection a daunting problem. 鈥淣ow that it seems we can focus
on single MiHAs, this will be a lot less like shooting in the dark,鈥� he says.