The New York Times reports that genetically altered T cells have been successfully deployed to fight chronic lymphoblastic leukemia (CLL).
It could reasonably be imagined that cancer is nothing more than a defect in the immune system. It is assumed that everyone occasionally grows rogue, potentially-cancerous cells, but that these are routinely recognized as such by the immune system, and targeted for destruction. When a cancer cell takes hold and begins multiplying, it means the cell has successfully evaded the immune system’s defenses. Perhaps the cell is especially clever at shielding its nefarious intent from the roving immune system warriors, the T cells, that destroy or tag for destruction cells infected with viruses. Viruses operate very much like cancer cells, hijacking the intracellular replication machinery, and modifying the DNA so that the cell forgoes whatever is its normal function for the purpose of making viral copies. Cancer cells also have rearranged stretches of DNA, particularly in the areas that code for apoptosis (cell death), which is why cancer is so deadly to its host body. A cancer cell is the only extant evidence that it is at least genetically possible for a cell to live forever. Gather enough of them together, and they’ll finally die, but only for having killed their source of sustenance. Sort of like humans infecting the planet.
Scientists have now successfully (in two out of three tries) altered patients’ T cells so that they will do to cancerous cells what they naturally do to virus-infected cells. Using defanged HIV viruses to deliver genetic alterations to a patient’s T cells, scientists made them into cancer killers for the particular cancer involved (CLL). After promoting multiplication among this genetically altered colony of T cells, they re-infused them into the patients, and the T cells proved able to seek out and destroy the cancerous cells. Thus the therapy works in principle, but there are some caveats.
First, CLL is a cancer of the B cells. B cells are one weapon, but a very important one, in the immune system arsenal that is employed to fight infection. The B cell’s main job is to produce antibodies that tag the surface of an invading cell for destruction. Without B cells and the antibodies they produce, the body is more susceptible to infection, particularly of the bacterial variety. The genetically reprogrammed T cells in the study were programmed to kill all B cells, not just the cancerous variety, and if the treatment works, would continue to do so for the rest of the patient’s life. After infection-fighting (which is what the T cells were programmed to believe they were doing) subsides, a certain subset of T cells will hang around indefinitely as “memory” cells in case the infectious agent returns. This is why, for instance, vaccines work for several years, sometimes for life, in imparting immunity to a disease. Thus the patients with these altered T cells will basically never again have B cells, which is not necessarily deadly, but means they will always face a greater risk of suffering a deadly infection. CLL is also a deadly infection of sorts, but more predictably so than some ephemeral possibility of a deadly infection that comes with B cell depletion, so perhaps the bargain is worthwhile.
The other problem is applying this sort of therapy to other, non-B cell cancers. B cells are unique little creatures. They have (along with T cells) the ability to rearrange their own DNA to best configure themselves to fight pathogens. They also have unique cell surface markers, that at least one chemotherapy drug (Rituxan) has been developed to exploit, much in the same manner as this T cell therapy. Rituxan is a monoclonal antibody that attaches to a cell-surface marker unique to B cells, targeting the cell for destruction by T cells and other immune system agents. It, too, kills all the B cells, but does so only until the antibodies are used up or filtered away by the liver or kidneys. Though produced in a culture in much the same manner as the altered T cells were grown after alteration, it is not a complete living cell, capable of independent reproduction inside the body. It is probably the case that the CLL patients upon whom this therapy was tried had already used Rituxan to the limits of its capabilities. Rituxan is used for a number of B cell-mediated problems, including lymphomas, post-transplant lymphoproliferative disorder and certain autoimmune diseases.
Other cancers, and tissues in the bodies, don’t have such a unique marking system as do B cells, so identifying the proper marker to identify cells for destruction could be a lot trickier with cells other than B cells. Presumably this is why only one monoclonal antibody of Rituxan’s type has thus far been successfully developed, and is also why figuring a way to make T cells into, for example, pancreatic or lung cancer fighters, is apt to be a great deal more complicated than this partially successful experiment might imply.
The one patient whose personal story was highlighted in the article, and for whom the therapy has thus far provided a complete remission, said his doctor offered some profound advice once it appeared the experiment had worked:
“She said, ‘We don’t know how long it’s going to last. Enjoy every day,’ ” Mr. Ludwig recalled.
“That’s what we’ve done ever since.”
That seems to be pretty good advice, no matter whether one has had cancer or not, no matter whether a cancer therapy has proved successful or not. No doctor has ever saved a life. Mr. Ludwig, like all other patients treated by doctors in all times and all places, will one day die. Why does it take a close brush with death to understand that one’s days are limited? A matter for another post.