T-cell engineering for cancer treatment

Several patients brought me news articles this week about today’s New England Journal article that describes use of a sophisticated bit of molecular biology to re-direct the body’s immune response to attack cancer. The researchers essentially took a small number of T-cells out of a patient who was in trouble with a form of leukemia called CLL and infected them with a virus that converted them into killer cells that could multiply and continue the attack. The patient has gone into complete remission, however there are risks and side effects, some of which you can read about here.

In the news articles, mention was made of how this might be useful for treating prostate cancer among others. I think it is definitely worth watching, but a long ways off. First, the target needs to be identified that would be unique to the prostate cancer cells. PSMA is one such target, but it is expressed on other kinds of cells as well, and “off target” toxicity could be significant. Second, the immune system is “pre-designed” to respond to killer T-cells. Lymphocytes are the complex cells that both make antibodies and kill viruses. However, if there was not a damping system in place, your first tetanus vaccination could mean that all of your lymphocytes would keep responding to that antigen forever, not get ready for your next bout of influenza. (This is one of the problems with ipilumimab, which, although it blocks the damping system, results in the body beginning to attack itself.) Finally, the technology of “designer T-cells” for each patient would be even more complex than the currently available system used to make sipuleucel-T (Provenge) and therefore that much more expensive. We can’t use “just anybody’s T-cells”, because your body would recognize them as a graft and reject them, much like the risks with kidney or liver transplants.

So, science marches on in marvelous ways, and there is always new hope for treatments. That’s the fun of being a clinician/scientist in this era. But it is also the frustration for patients, which I fully understand.