T Cell triumph
IMMUNOTHERAPY MAY HAVE FINALLY TURNED A CORNER BY DIANE MARTINDALE, 2003
Despite the recent success, immune cell therapy Is still highly
experimental. Side effects were serious In some cases: they
Included vitlilgo (white patches of skin where normal pigment
were attacked by the tumor infiltrating lymphocytes) and
opportunistic Infections. This is not like a drug you can
off the shelf. Every
cell we give is basically a different drug because it’s unique to that patient. And every patient has a different kind of tumor,” sags Steven A.
Rosenberg of the National Cancer Institute, who is still trying to understand why the therapy works in some and not
in others. Rosenberg thinks
it will be at least two years before the therapy is ready for other types of cancer patients.
Immunotherapy for cancer is a targeted treatment that uses a patient’s own immune cells to attack and destroy tumors. Highly touted when it was conceived in the early 1980s, the
approach has met with little success. Now researchers think they may have gotten over the hump: they have successfully
treated several cases of a deadly skin cancer with immune cells taken from the patients, grown in large numbers in the laboratory
and then given back to them. “We can now repopulate the body’s immune system with cells that fight the cancer,”
says Steven A. Rosenberg of the National Cancer Institute, who pioneered immunotherapy.
The idea is to exploit a
subset of T cells, the so-called tumor-infiltrating lymphocytes (TILs), found deep inside cancerous tissue. These killer
T cells attack the rapidly dividing cells and provide a natural protection against cancer. But the body seldom makes
enough to keep the disease in check.
Rosenberg first isolated
and grew TILs and gave them to patients in the 1980s, in a process called adoptive T cell therapy. Although the T cells
retained their antitumor properties, they did not proliferate or survive long enough in patients to kill their tumor cells.
The recent success came when Rosenberg’s team altered its method in two crucial ways. First, the scientists improved
the way antitumor T cells are generated. TILs were isolated from multiple samples of each patient’s tumor and grown
in the lab. The group then tested up to 50 different samples against each patient’s cancer cells and chose the
most reactive T cells to expand and reinfuse into the patients. Previously, cells were simply extracted from the
tumors without any type of selection.
Second, the researchers changed
the way patients are prepared before the treatment. This time subjects underwent robust chemotherapy to wipe out their
immune systems temporarily and thereby make room for the incoming tumor-killing T cells. The procedure may have removed
suppressor cells (made by the immune system or the tumor), which prevent T cells from proliferating, Rosenberg says. After
the reinfusion, patients received repeated doses of interleukin 2, a potent immune system hormone that stimulates the growth
of T cells.
The study relied on 13 individuals
with advanced metastatic melanoma, a skin cancer that eventually spreads to other organs.
The patients, who had exhausted all other treatments, including surgery, received on average 80 billion of their
own TILs—enough to give them a new immune system. As of December 2002, 10 of those subjects were still alive: six had
major remissions of their cancer, and four had some of their tumors shrink.
Analysis of patients’
blood and tumor samples showed that the TILs multiplied and then attacked the tumor tissue. “In the past when we transferred
cells, maybe 1 or 2 percent survived,” Rosenberg explains. “Now we have 80 percent that survive for months,
and when that happens the cancer disappears.
“The good news about
Rosenberg’s work is that as a proof of principle, it’s extraordinary,” says Robert A. Figlin, an oncologist
at the University of California at Los Angeles School of Medicine. “The bad news is that it’s not easily extrapolated
to a large group of patients.” Moreover, “we are asking a lot of these T cells to treat patients with very large
tumor burdens,” says Cassian Yee, an immunologist who has developed a similar T cell transfer therapy
at the Fred Hutchinson Cancer Research Center in Seattle. “The T cell therapy might be more effective with smaller
tumors and with repeated treatments over time.
According to Figlin, the
key to immunotherapy is selecting the right patients. “There will be a smaller number of patients that have a higher
response, and not the other way around,” he explains. “That’s the reality until we understand the subtleties
of the immune response.
Diane Martindale is based in Toronto.