There's an excellent overview at Science of the work of David Porter and Carl June at the University of Pennsylvania on T-cell-based cancer therapy. It turns out that when the dramatic reports came out on their first three patients, the team was out of funding and trying to see if they could get someone interested. They did:
. . .Porter and June weighed their next step. They were itching to test the cell therapy in more people with leukemia, and to do that they needed money that they didn’t have. “We basically decided that we would just publish with three patients,” June says. Getting the word out, he hoped, could shift the dynamic in their favor. Porter was game to try, but skeptical that any reputable journal would accept a paper with an n of 3.
He turned out to be wrong. The New England Journal of Medicine welcomed a report about Olson and his mouse dose of T cells. Science Translational Medicine, Science’s sister journal, snapped up a manuscript detailing all three patients. The papers were published simultaneously on 10 August 2011. . .Porter was en route to vacation in western Maryland with his family when the embargo lifted. His phone started ringing. “I was in the car for 8 hours that day,” he says. “I spent 8 hours straight on my phone, answering e-mail, answering phone calls. It was a story that took us all by surprise. It kind of went viral.” June fielded 5000 requests from patients and their families for the therapy. Eight hundred media outlets worldwide covered the story.
And the funding reappeared, as well it might. Now the problem is turning this into something that can be used routinely, and that is nontrivial, as we technical types say. T-cell therapy is patient-specific. You don't just start treating everyone with injections out of the vials that you keep in the fridge - every patient is a new experiment, and the process starts from scratch. That means that many sources of error and variability that are ironed out with a traditional drug therapy are still going to be present, every time, for every person, and it also means that the cost is going to be high. But it may well be worth every bit of the trouble and expense.
The article gives a good look at how hard it is for a discovery like this to be born. The first person to try modifying T cells as an anticancer agent was probably Zelig Eshhar at the Weizmann Institute, back in the 1980s. Then a few other labs picked up the idea, notably Michel Sadelain at Sloan-Kettering, Steven Rosenberg at NCI, and Malcolm Brenner at Baylor, but technical difficulties slowed things down at every turn. Isolating the T cells reproducibly, inserting new genes into them, figuring out what genes to insert, getting everything successfully back into a patient - each of these steps took years of work and frustration.
Success came as everyone narrowed down on the CD19 protein on the surface of B cells. Those were attractive targets, because you can actually survive without them - which was a key hurdle, because once you unleash the T cells, they're probably going to kill off everything they're targeted for. It turns out that the CD19 marker is basically universal in B-cell leukemias, so this looked like the best targets on several grounds. There were actually four other trials (using very similar approaches) running at other centers when Porter and June got going.
But the combination of stimulatory signals and the choice of vector in the Penn trials set off the extraordinary clinical effects. There was no way to know this - in fact, some other approaches looked a bit more promising. But that's clinical research, and that's oncology, for sure.
Unfortunately, but predictably, there have been legal problems. St. Jude and Penn are involved in lawsuits about prior research agreements, and whether the current therapies are covered under them. I assume that this will be worked out, to the enrichment of a phalanx of lawyers, but it's unfortunate. It doesn't seem to be slowing anyone down much, though, which is the good news. Trials are underway all over the place on variations of this idea, and the Penn group is about as busy as they could possibly be:
Still, physicians like Porter and Grupp are mindful that this isn’t life-changing for every- one. “When I’m doing informed consent with these families, the first thing I say is, ‘Forget everything you’ve read about this,’ ” Grupp says. “Nothing could possibly be as promis- ing as the various articles about this make it seem.” Only four people, including Emily, have been followed for more than a year. A looming question is whether CAR therapy can work in solid tumors, and June and others are opening clinical trials to try and find out.
Nearly 3 years after the summer that changed everything, the Penn group is still working flat out to keep up: enrolling as many patients on the trials as they can, working with drug regulators to discuss how best to study the cells with an eye toward approval, collaborating with Novartis to train their employees and streamline the cell-generating process.
This all should be seen in a larger context of immunotherapy, too. People have been trying to recruit the immune system for years in the fight against tumor cells, with mixed success. But we may be just on the verge of knowing enough about what we're doing to get more of these to work. At this point, it would not surprise me if immune system approaches become the dominant form of treatment for several types of cancer over the next 25 years. The next few years will tell us.