By Tom Corwin| Staff Writer

Saturday, December 08, 2007

Yukai He has to badge his way through three locked doors to get into
his lab at Medical College of Georgia Cancer Research Center, steps
that he jokes about circumventing. The virus he works with, the
lentivirus, isn't a biological threat. But one day he and MCG
researcher David Munn would like to make it part of a potent cancer
vaccine that would be part of a sophisticated way to knock out tumors.

The lentivirus is a hybrid that has had all of the virulent proteins
that make people sick removed. It is now merely a vehicle, called a
vector, for delivering something inside of a cell. In this case, it
would be a protein taken from a cancerous tumor.

Scientists have been working diligently for decades on a cancer
vaccine, trying to train the immune system to recognize a cancer and
dispatch it, but none have worked. There are probably several reasons,
one of which Dr. Munn has been studying for the past 10 years. It is a
chemical called indoleamine 2,3-dioxygenase, or IDO for short.

Dr. Munn and Dr. Andrew Mellor first identified it as the mechanism
that protects the developing fetus, and its foreign genetic material
from the father, from the mother's immune system. Unfortunately, many
tumors also use it to create a "tolerance" for themselves from the
immune system. The first cancer patient to try a drug that suppresses
IDO was enrolled last month at Moffitt Cancer Center in Tampa, Fla.,
and the IDO suppressor will also begin early clinical trials within
the next six months at Vanderbilt University in Nashville.

The suppressor might not be sufficient to get rid of a tumor, Dr. Munn
said.

"It might be that taking away all of the brakes still isn't going to
give the train a push forward," he said.

Dr. He is the first vaccine recruit to MCG, with the idea of
stimulating the immune system to recognize and attack the tumor. The
problem with previous vaccines is that, even when they stimulate a
potent response, the tumor is unfazed.

"There have been a couple of papers in the last year or two pointing
out the sad fact that you can get really, really good responses to
these vaccines and the tumor still doesn't shrink and go away," Dr.
Munn said.

That is what led Dr. He to leave the University of Pittsburgh and come
to MCG for four months to work on the IDO problem with those he called
"the pioneers in the field."

The vaccine approach, using the lentivirus, should have some
advantages over other approaches that used different virus delivery
vehicles, such as the adenovirus that causes many common colds. The
problem with using that virus is half of the population already have a
neutralizing antibody to the adenovirus from a previous infection, Dr.
He said.

"So in that case, in 50 percent of people it won't work," he said. The
lentivirus is a hybrid that the immune system hasn't seen before.

Another problem with the adenovirus vehicle is it can provoke an
immune response to itself instead of the cancer protein it is trying
to deliver, which derails the immune response, Dr. He said. The
lentivirus is innocuous enough that it won't provoke an immune
response on its own, he said.

Yet it appears to be able to infect a key type of cell that can train
the killer T cells of the immune system to recognize proteins, in this
case proteins to the tumor, and it appears to have a long-lasting
effect, Dr. He said. The virus also cannot reproduce itself inside a
cell.

"That's a safety point," Dr. He said.

If the IDO inhibitor proves to be nontoxic and well-tolerated by
patients, which Dr. Munn suspects it will be, it can be tried with
conventional chemotherapy. That could lead to adding immunotherapy.

"That will create what I think of as a window of opportunity for the
immune system to respond," Dr. Munn said. "But it doesn't necessarily
give it much of a kick to respond."

"And the (cancer vaccine) probably has a better chance of really
kicking off the immune response," Dr. He said.

"This is going to wind up being a multipronged approach to this
disease," Dr. Munn said.

MCG is looking at other centers to see whether its combination
approach can be combined with other drugs and therapies, he said.

"There's a lot of interest in the field right now in combining
different people's individual single strategies together into
rationally designed regimens," Dr. Munn said. "MCG has an opportunity
to become a major player in that area in part because we have a
reputation for our particular little area that we work in, which is
the IDO (approach)."

Reach Tom Corwin at (706) 823-3213 or tom.cor...@augustachronicle.com.

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