When a virus infects your body, T cells hunt down and kill the infected host cells. Now imagine if they could do the same for cancer, zeroing in on tumors and eliminating them.
Dr. Richard Junghans, chief of surgical research at Roger Williams Medical Center, has modified T cells to create “designer T cells” that successfully killed cancer cells in animal trials. Now the U.S. Department of Defense Breast Cancer Research Program has awarded him and his team nearly $6 million to try it in human patients, targeting metastatic breast cancers.
The grant, an “Impact Award” – from a program that supports projects “with the potential to have a radical, revolutionary impact” in breast cancer treatment, was a rare coup: Not a single applicant in 2007 succeeded, and only two, including Junghans, did last year.
Junghans answered questions about the grant and his work.
PBN: What do you mean by designer T cells?
JUNGHANS: Designer T cells are patients’ own T cells that have been genetically modified to fool them into thinking that the cancer has a virus infection. T cells evolved to kill our own cells, but those that are infected with viruses. … Unfortunately, T cells don’t see cancer as being foreign, for the most part, so they just treat it like it’s normal tissue. Our trick is to go into the machinery of T cells and modify it in such a way that we create new receptors to educate them to go after the cancers as if they were virus-infected. There’s a number of ways to do that, and we will approach several over the five-year period of this award.
PBN: So where are you with this?
JUNGHANS: We are actually ready to treat our first breast cancer patients and will begin during the summer, I expect, to do the first treatments. We’ve done animal studies, and we’re actually completing a safety study with the designer T cells in general cancer patients – so far it’s been safe, but we’re going to be doing other things to increase the effectiveness to attack the cancers and chase them down wherever they are in the body.
PBN: How do you do that?
JUNGHANS: Many people know about a protein in breast cancer called HER2, but there’s a protein that is even more common in breast cancer called CEA. Antibodies against CEA don’t do anything, but it’s a very good target for us to use with T cells, because T cells have their own little weapons on board. All that the T cells have to do is recognize the cancer and once they unleash their weapons, the cancer cells are destroyed within minutes.
So what we’ve done is geared up T cells that will go after cancer cells that express CEA on them. That accounts for a third to half of breast cancers, but that’s still a lot more than HER2, where the fraction is only a fifth to a quarter. And if the cancer has HER2 and is spread throughout the body, the antibodies won’t cure it; they will just slow it down, whereas we’re really going for a cure with these designer T cells. Our whole aim is to be able to eliminate breast cancer cells wherever they are in the body. That’s why we’re gearing up so heavily to do this, taking women who are otherwise certainly going to die from their disease and try to cure them.
PBN: So what will the studies entail?
JUNGHANS: Our first study will be to use high doses of designer T cells and give them either without or with a growth factor called interleukin-2 (IL2). Our first test is going to be: Does this T cell growth factor lead to an improved function of these designer T cells, or do they cure the cancer even without the IL2? That’ll take about a year, once we get started.
Then the second experiment will explore using other growth factors, IL12 and IL15, which will make these T cells expand and possibly be more potent when we do give them to the patients.
There’s another protocol where we will use these cells where we’ll give high-dose chemotherapy prior to the T cells. That creates a space in the body and the T cells go in and say, there’s not many T cells around (because of the chemotherapy), so we’re going to expand. That will increase up to 100-fold the number of T cells that we infuse.
And then we’re doing a basic research component in which we’re looking at ways to make more advanced versions of designer T cells by putting in more signals into the cells. Everything I’ve told you so far uses the T cells we have, which the FDA has approved for use in humans, and which have been created and passed through all sorts of testing. … But we’re not going to rest that. We are going to initiate laboratory tests that will go on concurrently with these clinical tests to develop third-generation designer T cells which brings in new types of signals, new ways that these T cells can persist and act against the tumor.
PBN: How big a patient base are you going to be working with?
JUNGHANS: Over a period of five years we are looking at treating somewhere around 60 or 70 patients. Most of the patients will be treated at Roger Williams, but when we are in the Phase II study portion of the plan with an established protocol of treatment … we could treat at more than one institution, and we may. … Dana Farber and the M.D. Anderson Cancer Center at the University of Texas are interested in this, for example, so we may get some collaborations to treat patients at distant sites for part of this study.
No one’s done this yet in humans. There’s maybe half a dozen clinical trials around the world using designer T cells, none specifically for breast cancer, we have one of the most advanced constructs anywhere that are approved for human testing. So designer T cells are just emerging as a new way of treating cancers.
I think within five years we’re going to see a designer T cell agent somewhere approved as a new “drug” for routine use in human cancers. And all that patients will have to do is go to a blood bank, and the blood bank will draw a unit of blood, and they’ll ship it to a facility that will purify T cells, modify them, expand them, put them in a bag and send them back and they’ll get them infused at their home oncology clinic. We’d be able to do thousands of patients every year, hopefully to reduce significantly the number of patients who have to die from breast cancer every year. That is the goal of our research.