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A BIT of genetic tinkering can turn the immune system鈥檚 sentries against
invasion into crack troops, say researchers in the US.

Dendritic cells have an unrivalled ability to stimulate an immune response
and are already being tested as live 鈥渧accines鈥� in clinical trials. They pick up
foreign proteins and show them to other immune cells, along with various
鈥渃o-stimulatory鈥� proteins. Killer T cells then seek out and destroy any invading
cells displaying these foreign proteins.

So by harvesting dendritic cells from patients and loading them with proteins
from tumours or viruses, researchers hope to develop immunotherapies for
diseases as different as cancer and AIDS.

But Jeffrey Schlom of the National Cancer Institute near Washington DC and
his colleagues wondered if dendritic cells had even greater potential. They
infected dendritic cells from mice with a bird virus called avipox that had been
given genes for three co-stimulatory proteins鈥擝7-1, ICAM-1 and LFA-3. The
engineered cells produced three times as much of these proteins as normal.

When the team used these cells to immunise mice against a foreign protein,
the result was dramatic. Mice given the genetically engineered cells had over
six times as many killer T cells as mice immunised with normal dendritic cells,
鈥淭his shows we can really turbocharge the immune system,鈥� says Schlom.

鈥淭he concept that you can still improve on these cells is very important,鈥�
says Kim Lyerly, a cancer researcher at Duke University in North Carolina. 鈥淚t
justifies exploring this approach in clinical trials.鈥�

Ronald Levy, head of the cancer division at Stanford University, agrees. The
method is very practical, he says. The avipox virus cannot replicate in human
cells, so it is unlikely to spread to other cells in the body. And many leading
clinical labs are already adept at handling avipox. 鈥淚t鈥檚 something we all know
how to do,鈥� he says.

Schlom says he has produced an avipox virus that carries human versions of
the co-stimulator genes with the help of his collaborators at Therion Biologics,
a biotechnology company based in Cambridge, Massachusetts. They hope to
have approval for a safety trial for cancer treatment within a year.