Research in Gene Therapy

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Research in Gene Therapy




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.  


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