Word got out late last month that, after watching their new cancer therapy eradicate several disease strains in mice, researchers at Wake Forest University were . The scientific community—and the Web—were abuzz. Biochemist controversial idea centers on pulling out healthy, cancer-fighting white blood cells from healthy patients, then injecting them into someone with cancer. His mice-and-test-tube success is the basis for planned clinical trials, but the established medical community isn't quite ready to embrace his approach. But patients, Cui (pictured above at left) told PM in an extensive interview, are taking him up on the offer to pay for their own experimental treatment—one of many aspects of this research that deviates from medical norms. —Phaedra Hise
How did a single mouse start this research?
We started from one cancer-resistant mouse in 1999 and bred thousands of offspring who share the same resistance. We realized ... this could be a very good shortcut into the human therapy. But our approach is not completely in the arena of science because we jump over too many incremental steps, so that's why if you review the general field of cancer treatment, especially cancer virologists, they won't like his very much. We skip over all the incremental steps—"what is a gene, what is a mechanism"—but in medicine you don't really need that to develop a therapy. A physician will tell you it's wrong, but the important thing for us is that it works. As long as it works, we don't really care about how it works. Ninety percent of medical progress is made by the empirical approach rather than rational design. Rational design is, basically, when a human comes up with an idea about how nature should work and then proves that the idea is correct, before you actually develop something. But in empirical approach, you simply make observations and learn from nature: what happens, how you can take advantage, and then simply copy that. That is what we have done.
How does this apply to your research?
First, we had cancer-resistant mice and asked, 'What can we learn from it?' The reason it's resistant is because it has very different white cells. So then that immediately prompted the concept of therapy, because you can easily transfer white cells. You can extract them as a therapeutic agent and give them to another mouse. It's a therapy. It's much better than to find the gene. If you find the gene, then you have to understand the mechanism, and you have to find a way to put the gene into the cell, into all the cells you want to, and that would not work very easily. The technology as we speak right now is not really mature for that area. You might have to wait another 10, 20 years before that technology catches up with the concept. However, what we found is a cell as a therapeutic agent, so why not go ahead and see how it works. It worked really well in mice, so the next question, very obviously, is can we find a similar cancer resistance for humans as a donor for a therapeutic agent. And the answer is yes, we did find quite a few of them
So you don't understand the mechanism at work here?
A lot of people don't like this because they said I have not a single idea of how it works. And I said, "Why should I?" If I can already go into therapy, why should I spend so much time now to find out how it works? That dispute was with the establishment, that's why this trial has not been funded.
So how did you get it funded up to this point?
There is some private funding and the university put some funding into it. And also, at early stages when we studied the mechanisms of these mice, we had one Mitchell Cancer Institute grant, several small grants from Cancer Research Institute. But they all stopped funding me. It was kind of a strange situation. I thought it was our common goal to come up with a new weapon to fight cancer, but the moment I announced I had a new weapon to test in real human cancer situations, everybody shied away. We're still looking for funding, and writing grants that get rejected. I think at this moment, we just say, there are a lot of cancer patients who want to pay for themselves, and for them, they can't live, their money means nothing, so it's an easy justification for them to spend the money ($100,000) they have to try to save their own lives.
And that's enough to fund the clinical trials?
No, they could fund their own treatment.
If each person pays the $100,000 fee, then that is enough for you to go ahead and do a clinical trial?
And how many people do you have to get before it's considered a statistically significant trial?
Well, our number is 22. That's how many we hope to get. But right now our Web site ( http://www1.wfubmc.edu/LIFT/ ) has over 100 patients signed up. We're trying to find the solution for a very profound need. We have over 600,000 people in this country dying of cancer each year. So for them there are no other options available to them because they are running out of all of them. The only thing for them is to wait for the inevitability. And instead of doing that, now we have provided hope, no matter how small it may be at this moment.
So, these cancer-resistant blood cells are something that a person either has or doesn't have? Or is it something that a person can have at a certain point in life and then maybe not have at another point?
Oh yes, it's a very dynamic activity. Not everyone is the same. Someone has higher activity than the others. Our fundamental theory about this activity is that it is much lower in cancer patients than in healthy populations.
And this treatment is something that could ostensibly treat any type of cancer? We don't know until we try it, but we're going to try all types of cancer even at this stage, except brain mass or brain tumor and leukemia, so these are two categories that we want to avoid until we get some safety data and then we can consider later on.
Where do you get the cancer-fighting white blood cells in people?
All we need is for donors to come in and donate 20 cc of blood and we will look for the ... criteria. We wish that we could build a donor registry first rather than look for a specific donor for every patient who comes in. If we have a donor registry, we can just pick and choose from existing people who have been matched already. You need a blood type match and also sometimes we have to mismatch. That's to make sure that you don't have close blood relatives to donate for you. That will make your donor cell linger in your body and cause graft versus host disease (GVHD).
Please explain GVHD for us.
That means the donor cells, instead of killing cancer cells, they start to attack healthy cells in the recipient. It's a very nasty side effect of transfusion-related treatment. It gives you fever blisters and gastrointestinal tract infections, very nasty. It does kill people. But most people react with mild GVHD and it's quite manageable. For most cases, if you say the tradeoff is to manage your own GVHD versus malignancy, I think over 90 percent of people would say I would rather deal with GVHD.
How does this compare with currently available treatments?
Chemotherapy does cure several types of cancer, some types of leukemia, lymphoma, Hodgkin's, testicular cancer, and they're all very responsive to chemotherapy at very high rates. But unfortunately, a lot more cancers won't respond to therapy at all. We are hoping this radically new idea will provide some complement to general treatment so that people running out of options with conventional therapy can give this a shot and see what happens. At this stage we don't really want to compete with conventional therapy, not taking away the opportunity because some of the patients can still benefit from chemotherapy. So the good thing is that in the worst scenario, if it's not effective, if it flops in terms of a therapeutic concept, at least they won't harm the patient like chemotherapy would.
How long will this study take?
We hope we can probably finish within two years. Right now we don't have a lot of new issues [that have] come up to deal with all the paperwork along the way, but I think we're moving forward really fast. I hope that we'll get real transfusion in a month or two, but I could be too optimistic ... Our current operation scenario is that we have no sponsors and the patients have to pay for themselves. Down the road, we do have some paperwork in the making that has a financial sponsor to come in. I don't know when that will happen, maybe a month or two, maybe six months, who knows.
How do you envision the study progressing? If we treat the first 10 patients, and the response is overwhelmingly positive, like we predicted from the mice study, we could stop the trial and move into the next phase already. The next phase is to try and see which type of cancer will respond to treatment better than the other types. And basically, it's an accuracy study. Maybe at a certain point, we will have to move into double-blind. We have a pretty good idea about cancer patients, when they're going to die! Sometimes we could be wrong, and you see the patient saying the doctor told me six months ago and I'm still alive, look how bad he was, and there are exceptions. You look at the entire group as a whole and the physician's estimate is always right on spot. As a group, you draw the curve, and you usually don't vary them at all. So if we move into that stage, initially we might do open label study and try to convince ourselves that we don't need a control group. But if we later want to convince other people like the FDA or other scientists, then we'll have to double-blind with a control. One group of people on standard therapy, one group of people on new therapy and see who lives longer.