Gene Therapy Brings Three Cancer Patients Back From Death's Door; What Now?

By Veronique Greenwood
Aug 11, 2011 7:06 PMNov 5, 2019 4:33 AM


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Modified immune cells decimated chronic lymphocytic leukemia, scientists found.

What’s the News: Striking results in a very small study have got the web a-buzz about a new cancer treatment: With three leukemia patients at the ends of their ropes, scientists modified some of their immune cells with a gene that enabled them to hunt down cancer cells. Remarkably, the treatment wiped out more than two pounds of tumor tissue in each patient, and the three have now been in remission for a year.

But what weight does such a small study carry, what about the side effects, and what do these results mean for people with other cancers?

How the Heck:

  • First, the team removed immune cells called T cells from each of the patients, who had chronic lymphocytic leukemia, a cancer affecting blood cells called B cells.

  • They had a lab-built virus insert a gene for a protein that would recognize a specific tag appearing only on the surface of B cells, as well as genes for two other proteins involved in the process, into the T cells. (This kind of treatment, called gene therapy, has been of interest in treating cancer for some time.)

  • The team then injected each patient’s own T cells back into their blood, where they began attacking the cancer cells, whose death the team confirmed with blood tests and other measurements.

  • Taking counts of the patients’ cells, they estimate that each modified T cell must have hunted down and killed a thousand cancer cells. Before the treatment, the ratio of cancer cells to normal cells in the bone marrow was horrifying: in one patient, 170 out of 200 were cancerous. Afterwards, that number was only 2 out of 200.

  • The modified T cells have remained in the patients, even months after the treatment, potentially contributing to the patients’ ongoing remission.

Not So Fast:

  • Cancer patients are routinely exposed to treatments much worse, at least in the short term, than the disease: killing cancer cells means killing a lot of healthy cells. With this treatment, nearly all of the patients’ B cells, healthy and otherwise, were destroyed, and even months afterwards the B cells had not recovered. Since this is the class of immune cells that produces antibodies, this loss could be quite serious in the long term, though all the rest of the patients’ cells were unharmed.

  • The team also notes that the mass murder of cancer cells provoked a serious response: the patients’ bodies were flooded with detritus from the bursting cells and inflammatory molecules produced by the immune system, some at 160 times the normal levels. Their kidneys were in acute distress, and at least one had to be hospitalized because of it. The researchers note that they are really going to have to pay attention to this when they’re designing larger studies. Maybe the injections will be spread out more, or maybe not as many altered immune cells are required.

  • Additionally, one of the most exciting things about this study—that the T cells stay in circulation and may keep destroying any cancer that crops up for years—makes it quite different from, and possibly riskier than, most cancer treatments, which usually are purged from your body in a matter of weeks. That means that the follow-up work to figure out what the T cells are doing, and whether they might be somehow dangerous in the long term, will be substantial. What, for instance, will the indefinite lack of B cells mean? The FDA will need serious reassurance on these points, especially since gene therapy carries a risk of causing mutations in modified cells that might eventually turn them cancerous over the patient’s lifetime.

The Future Holds:

  • The next step for the researchers is much, much larger studies, incorporating the points raised above. For all intents and purposes, this report is a case study, without the statistical power required for assessing a treatment’s usefulness in the population at large.

  • Researchers who focus on other cancers may also find it difficult to translate this success to their own patients: this team was able to make this work because they knew exactly what surface protein to target. As they point out in their report, we don’t have analogous information for many other cancers. And ideally, we’d find proteins that are specific to the cancer, not to the cell type, to avoid the problem this team is facing with B cells. So get cracking, all you budding researchers!

References: Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia. David L. Porter, M.D., Bruce L. Levine, Ph.D., Michael Kalos, Ph.D., Adam Bagg, M.D., and Carl H. June, M.D. New England Journal of Medicine, August 10, 2011 (10.1056/NEJMoa1103849).

T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia. Michael Kalos, Bruce L. Levine, David L. Porter, Sharyn Katz, Stephan A. Grupp, Adam Bagg and Carl H. June Sci Transl Med 10 August 2011: Vol. 3, Issue 95, p. 95ra73. DOI: 10.1126/scitranslmed.3002842

Image credit: Wikimedia Commons

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