WEDNESDAY, June 18 (HealthDay News) -- Patient "Number Four,"
taking part in an experimental melanoma treatment program at the
Fred Hutchinson Cancer Research Center in Seattle, was a very lucky
man.
After receiving an infusion of his own, fortified immune system
T cells, the man's melanoma, which had already spread to a lung and
to a lymph node in his groin and had not responded to other
therapies, went into complete remission.
Researchers reporting in the June 19 issue of the
New England Journal of Medicine say this is the first time a
patient's cloned T cells used alone have put an advanced
solid-tumor cancer into complete remission.
The man was followed for two years, at which time he was still
in remission. Doctors lost track of him after that.
"No way would we say this is a cure but he had a complete
response and, fortunately, for him, it lasted longer than just a
few months or weeks," said study senior author Dr. Cassian Yee, an
associate member at Hutchinson's clinical research division.
"I don't think this represents any standard of care, but I view
it as shining a light on the direction in which we perhaps should
be heading," said Dr. Louis M. Weiner, director of the Lombardi
Comprehensive Cancer Center at Georgetown University, in
Washington, D.C. "It's giving us some insights into what the
necessary conditions are for an anti-cancer immune response to be
effective."
Immunotherapy, which engages a patient's own immune system to
fight cancer, is an emerging art and science. The method holds the
promise of being much less toxic than other treatments, though
recent research has pointed out that it may not be as safe as once
hoped.
Research shows several instances when a patient's own immune
system kicked in to oust a cancer even without help from
sophisticated new technologies. Dr. Vijay Trisal, assistant
professor of surgical oncology at City of Hope Cancer Center in
Duarte, Calif., recounted two such cases: One, a woman whose
melanoma had spread to her lungs, brain and other parts of her
body, was stung by a bee and subsequently recovered not only from
the bee sting but also from the cancer. Two, a man with advanced
melanoma who stepped into a poison ivy patch and experienced a
similar recovery.
Similar happenings have been recorded for other types of
cancer.
"Maybe there were 10 cells in the body that were very good, sort
of a smart bomb against the melanoma, but they weren't enough,"
Trisal explained. "The bee sting or poison ivy multiplied these
smart bombs one thousand times so suddenly this army of 10 became
an army of a billion."
And that is essentially what the authors of the new study did,
collecting CD4+ T-cells from nine melanoma patients, isolating
single cells that they believed would target a certain protein on
the tumor cells, cultivating and enriching these cells, and then
re-infusing them into the patient.
Patient Four, a 52-year-old man, received five billion cloned
CD4+ T cells designed to go after the melanoma-associated NY-ESO-1
antigen. The new cells stayed in the patient's body for 80 days.
Two months later, the man's melanoma was gone.
The man received a higher dose than the first three patients but
the same or lower dose than the subsequent five patients. The first
three had no response at all while the later patients saw some
response, but none as dramatic as Patient Four.
"We don't know why he was the lucky one," Yee said. "Maybe it
was something specific to him or his tumor. Maybe he had a
low-level pre-existing response that we were able to augment."
And therein lies a major problem with immunotherapy as it exists
now. "We know this works but it's a shot in the dark," Trisal said.
"It works maybe in one in 100 people instead of one in 1,000 where
the body itself fights the cancer."
The question is how to make the process more efficient and
effective.
"Obviously there's a lot of promise for immunotherapy of this
kind but I think that we're several years away from making this any
kind of standard therapy," Yee said. At this point, the therapy
needs to be standardized to the patient and it can take months to
grow the required cells, during which time the patient's condition
could deteriorate dramatically.
"It would be helpful to try to streamline the process," Yee
said. "[Right now], we can only target a small fraction of
patients. What we're looking for in the future is to streamline
this process and decrease the time it takes to grow cells and to
see if we can target other antigens. This is a proof of principle:
Yes, we can use CD4+ clones."
More information
Visit the
American Cancer Society for more on
immunotherapy.