Research
in Gene Therapy
Transcript:
Guest: Dr. Michael
Nishimura – Surgery
Host: Dr. Linda Austin –
Psychiatry
Dr. Linda Austin: Welcome
to an MUSC research podcast. I’m Dr.
Linda Austin. I’m interviewing Dr.
Michael Nishimura who is Vice Chairman for Research in the Department of
Surgery. He is also a professor in the
Department of Surgery and he’s a program leader for the Cancer Immunology
Program at Hollings
Cancer Center. Let’s talk about your major areas of
research. I know you’re involved in a
good many things, but, right now, what’s getting you really excited about your
work here?
Dr. Michael Nishimura: By
training, I’m a cancer immunologist and my lab does gene therapy. We genetically modify lymphocytes in order to
treat patients, specifically T-cells.
This is actually a pretty exciting time in our field because there’s a
lot of clinical data now that is coming out that shows that by giving cancer
patients back their own T-cells, growing and expanding them in culture and
giving them back, they can actually have clinical responses. And the genetic modifications that we do will
enable many more patients to be treated.
So, we’re on the verge right now, actually, as of Friday, we opened our
Center for Cellular Therapy, which allows us to make clinical-grade cellular
products for patients. Being able to use
this facility to generate T-cells that can be used to treat cancer patients is
actually very exciting.
Dr. Linda Austin: That is,
really, very exciting. Now, just to back
up a little bit, describe what a T-cell is.
Dr. Michael Nishimura:
T-cells are a part of your blood cells.
They’re a part of the white blood cells.
They are principally designed to fight virus infections and various
other pathogens, various other infections that you would have. But, many years ago it was shown that they
can also be used to fight cancer. Many
patients that are able to activate their immune system and their T-cells in an
appropriate way can have an impact on them.
Dr. Linda Austin: So, in
this new program, now, are you at the stage where patients can participate in
clinical trials, in this research?
Dr. Michael Nishimura:
There have been a few clinical trials using the gene therapy types of
approaches and they’re not yet available here at MUSC. But, now, with the facility open, I’m in the
process of getting these trials underway, writing the grants to get the funding
to support them and getting all of the FDA approvals, all the regulations,
paperwork that needs to be done in order to do this kind of trial.
Dr. Linda Austin: What
types of cancers do you anticipate will be the first ones that you may take a
look at with this type of therapy?
Dr. Michael Nishimura: The
first ones, here, are going to be for targeting patients with melanoma,
metastatic melanoma. We have some very
active receptors that would be very good for putting into these patients’
lymphocytes for targeting that disease.
Melanoma is an important cancer and it’s a very aggressive disease. It’s not as common as some of the other
ones.
The second target we have is targeting hepatitis C. In terms of cancer, it’s one of the agents
that’s associated with hepatocellular carcinoma. There’s little to nothing that can be done
for patients that have hepatocellular carcinoma. There are no conventional therapies that work
very well. At the same time, it can
target hepatitis C infections.
Worldwide, about three percent of the world’s population is infected
with hepatitis C. And a high percentage
of those patients can go on to have cirrhosis of the liver and develop
hepatocellular carcinoma. So, we’re
actually pretty excited about that as a therapy.
Dr. Linda Austin: Well,
that’s tremendously important. So, walk
us through, then, what the clinical process would be for a patient when this
program is launched, let’s say somebody in a clinical trial who is actively
participating. They come in and they’re
diagnosed with hepatitis C, what would be the next step?
Dr. Michael Nishimura:
Well, these are not for patients that are newly diagnosed. So, it doesn’t matter whether we’re talking
about a melanoma patient or a hepatitis patient. For melanoma, the first therapies are to have
surgery. And, for primary melanoma, most
of the time, you’re cured from that.
It’s when you have advanced disease, when it spreads, metastasizes, gets
out of control, and you need some kind of therapy, something like this. With hepatitis, there are some treatments for
hepatitis. They’re not particularly
effective. About half of all patients
respond, which, given the number of patients, there are still a lot that don’t
respond.
So, what would happen is if you have a patient that has advanced
melanoma or diagnosed with hepatocellular carcinoma that would be associated
with hepatitis C, they would come in and, once these protocols are active, we
would isolate the white blood cells out of their blood, a process called apheresis. It’s a machine that basically returns everything
but the white cells back to your body so you don’t lose all your red
cells. Then, we take them into the lab
and we engineer them to recognize targets on those diseases, targets on
melanoma cells or on hepatitis C virus, and grow them a little bit in the lab
and then put them back into the patient with the goal of those lymphocytes
killing the tumor cells or the virus-infected cells.
Dr. Linda Austin: That is
very interesting. And there have been
preliminary studies showing that this is feasible?
Dr. Michael Nishimura:
There are a couple of clinical trials that have been published. The first one, actually, was a trial that was
conducted in Denmark,
using one of the receptors that we cloned, targeted a melanoma protein, and
there was one bona fide clinical responder out of it. This was an early safety trial, so we weren’t
expecting very many clinical responses.
But there were some hints that things were happening. And then, subsequently, the NCI group has
supported a study where they treated 17 patients. They had two bona fide responders in that
group. They’re continuing with some of
these. There are not many groups in the
world doing this kind of stuff, so it would be pretty novel for this area, for
MUSC.
Dr. Linda Austin: This is
very exciting research, but it’s very much in the preclinical stage. In other words, it’s going to be months, if
not a couple of years, before anything will be available for patients. Is that correct?
Dr. Michael Nishimura:
Well, here, yeah. I mean, that’s
absolutely true. Now that the Center for
Cellular Therapy is open, we have the means to make cellular products for
patients. We can move much faster toward
doing this, but there’s still a year or two of regulatory hurdles, and we have
to raise the funds to treat these patients.
These are experimental therapies.
Insurance companies don’t pay for them, so we have to write grants and
raise the money to do this. So, it’ll
be, probably, at least year, maybe a year and a half, before we’re in a
position to treat our first patient.
Dr. Linda Austin: So, we’re
thinking, maybe, earliest, summer 2010, more likely, 2011, or even later than
that?
Dr. Michael Nishimura:
We’re optimistic, maybe sometime in mid-2010, something like that.
Dr. Linda Austin: Right. And, if somebody listening is interested in
contributing to this, I think it would be very important for them to contact
our development office because it sounds like you really could use financial
support to get these trials up and going.
Dr. Michael Nishimura:
Yeah. The facility itself is very
expensive to maintain. It’s designed to
make patient-grade products, cellular products, which are clean, they’re safe,
and things like that. It’s a special
facility and it’s very expensive to run and maintain. And we have, really, one of the only ones in
this region. So, yes, we could use
financial support and, through Hollings, we’re always looking for assistance
and donors.
Dr. Linda Austin: Well, I
wish you well. It sounds like you are
really embarking on what will be a long journey and a very exciting one, to
offer some hope to patients who don’t have a whole lot of options right now.
Dr. Michael
Nishimura: Yeah, well, that’s the goal.
Dr. Linda Austin: Thanks so
much for talking with us.
Dr. Michael Nishimura:
You’re quite welcome.