This approach carries some safety concerns. Because of the special ability of stem cells to self-renew and differentiate into other cell types, the cells could theoretically start replicating out of control and form tumors themselves. However, Portnow and her clinical team did not see any such problems in an earlier pilot trial in which they administered just a single dose of the engineered stem cells into the brains of 15 cancer patients.
That pilot study was designed only to confirm safety — and it did — but it also showed early signs that the therapy could work. “We have evidence that the stem cells did in fact convert the prodrug to an active chemotherapeutic agent in the brain,” says Karen Aboody, the translational researcher at City of Hope who developed the therapy.
In Heil’s trial — which enrolled its second and third participants this past spring — the City of Hope researchers are now directly testing whether more cells, given for longer, can actually halt tumor growth without causing any undue harm.
A Platform Technology
The treatment is promising enough that research teams around the world are developing similar stem cell therapies that can target and eradicate cancers of the prostate, lung, breast, skin and other tissues. In Germany, for example, the Munich-based biotech company apceth has already treated patients’ gastrointestinal cancer with stem cells harvested from their own bone marrow and modified to convert a prodrug called ganciclovir. Among the first six patients treated to date, four responded favorably to the therapy.
Meanwhile, at the MD Anderson Cancer Center in Texas, Michael Andreeff and his colleagues are gearing up to launch their own stem cell trial for women with metastatic ovarian cancer. The bone marrow stem cells in this case come from a stock supply and are engineered to produce a protein that inhibits tumor growth called interferon-beta. Andreeff could treat the first patients as early as this summer. Trials of breast or melanoma cancer (treated with these same stem cells) could be next.
“This is really a platform technology — it can be adapted to almost any of the solid tumors,” says Frank Marini, who worked with Andreeff before moving to the Wake Forest Institute for Regenerative Medicine in North Carolina.
Still, the need for stem cell-mediated delivery is arguably greatest in brain cancer because most standard drugs cannot easily penetrate the barrier that separates the blood (through which drugs typically enter the body) and the brain. With an estimated 190,000 people globally dying each year from tumors of the brain and nervous system, and no significant changes in patient survival in the past two decades, “we need to do something different,” says Khalid Shah, a cancer biologist at Massachusetts General Hospital.
In one of his strategies, Shah is loading stem cells with cancer-slaying, or oncolytic, viruses. “The beauty of the oncolytic virus is that when the cell gets killed, it releases more virus, and that infects more cells,” says Shah. “There’s a chain reaction.” The viruses replicate in the stem cells as they migrate to the site of the tumor. Viral agents then burst out of the stem cells, infecting the cancer tissue — but leaving healthy brain tissue alone. (In one common system, the virus is engineered with a gene deletion that prevents replication in healthy neurons.) The cycle of cell death then starts all over again. While Shah’s work is promising, it’s only been tested in mice so far.
Sadly for Heil, the prodrug-converting stem cells weren’t enough. In February, after eight infusions of the new cell therapy, scans showed that his tumor had returned.
Heil is as pragmatic as he is fearless. “I knew I was going to die anyway, so I was willing to help for the betterment of medicine,” he says. For him, “nothing has changed” because of the trial. But for medicine, the experience could help bring stem cell therapies one step closer to cancer patients everywhere.
“We learned a lot,” says Portnow. “He clearly didn’t have any bad immune responses to the stem cells, so that’s encouraging.” Maybe with other patients, the treatment will prove effective, too.
[This article originally appeared in print as "Tomorrow's Cancer Treatment?"]