Can Your Stem Cells Kill HIV?

[Inchlingblue]

This is a very interesting interview, from of all places WJXT in Jacksonvile, with Jerome Zack, Ph.D., a Professor of Microbiology and researcher of stem cells and HIV.

Can Your Stem Cells Kill HIV?
Full Interview Transcript
POSTED: Friday, June 18, 2010

Jerome Zack, Ph.D., Professor of Microbiology, talks about using stem cell injections to treat HIV…

How do the blood stem cells you created work?

Dr. Jerome Zack: The idea behind the recent work was to engineer blood stem cells so that they would develop into lymphocytes, which are a mature blood cell type that can kill HIV.

Are those what T-cells are?

Dr. Zack: T-cells, yes. There are two types of T-cells – CD4 and CD8 cells. CD4 cells are the ones that get infected; CD8 cells are the ones that kill infected cells and stop virus replication. What we’re doing is engineering the stem cell to become a CD8 killer cell that could actually kill HIV infected T-cells.

How would you do that?

Dr. Zack: We have a gene for a receptor – a surface molecule on the T-cell – called a T-cell receptor, which we could introduce into the stem cell. We then model that by putting the stem cell into an organ called the thymus, which is actually found above your heart, and that is where T-cells develop from stem cells. When we put it through the thymus, that developed T-cells for us. They expressed the receptor that we had cloned into them and they were able to kill HIV target cells.

Do HIV patients lack these T-cells?

Dr. Zack: HIV patients’ immune systems are severely compromised. They may indeed be lacking functional T-cells to stop the virus. Often times, their immune systems are exhausted. The thought would be, if you could replenish their immune systems with new functional T-cells, you might be able to calm down the virus.

Have you done this in mice?

Dr. Zack: We’ve done this using human cells put through mice, and the mice were used as a culture vessel, if you will, to hold a human thymus. This whole strategy has to be done with the human thymus tissue there or the cells won’t develop, so we used mice that were engineered to have a human thymus within them.

What happened to the mice?

Dr. Zack: The stem cells were introduced into these mice. The stem cells will then go to the thymus, develop into mature, functional T-cells – we call these CD8 T-cells because those are the killer T-cells we want. We took the cells out and showed that they could kill HIV infected cells in the laboratory.

What’s your next step?

Dr. Zack: The next step would be to use a more robust model to show that we can actually do this – completely show HIV infection, as well as HIV killing within the animal model like a mouse. It would be a more advanced mouse system than we use right now. Subsequently would be clinical trials, but prior to that, there’s one caveat – HIV has a very, very fast mutation rate, so using one T-cell receptor would not be efficacious. One would have to have a library of T-cell receptors specific for pieces on HIV, so we would have to develop a larger library of T-cell receptors before this could be used clinically.

How long will it take before we you see that?

Dr. Zack: Putting a timeframe on HIV diseases is always a loaded question because every time we’ve tried to answer that question about any aspect of the disease, we’ve been wrong. I will say it would take several years to develop an additional library of T-cell receptors, a few more years to test it pre-clinically, and then we’d have to go to clinical trials. Clinical trials will often take, if successful, even seven years before it would go to actually be FDA approved, so we’re talking about 10 years before it can be used commercially if it was to work.

Is this a possible genetic vaccine?

Dr. Zack: Yes, so what we’re really doing is engineering the immune system using genetic engineering to respond to a foreign particle of choice, in this case, the AIDS virus. Basically, with our technology, we’ve shown proof of principle that you can engineer the immune system in humans to fight whatever infection you’d like, so we’re now also moving forward towards using this technique to fight cancer or other viral infections.
The whole field of stem cell research is booming. What we are using is adult stem cells or blood forming stem cells. The field of embryonic stem cells is also booming and we’re involving that as well, although this current work did not use embryonic stem cells, but clearly, for regenerative medicine, for fighting many diseases, including infectious diseases like we’re proposing, stem cells really are, in my opinion, the way of the future.

Where would you get the stem cells to treat an individual?

Dr. Zack: In our particular case, these were bone marrow derived stem cells from the same individual. There are ways to fairly easily make those cells leave the bone marrow and go into the peripheral blood, and then clinicians can isolate those stem cells. You would just treat them in a laboratory like we did in our experimental system and then re-infuse them back into the patient. This type of gene therapy trial has been tested many times. It’s very similar to a bone marrow transplant.
 
Continued . . .

LINK:

http://www.news4jax.com/health/23943304/detail.html

[Boze]

Awesome, thanks for posting. 10 years though...

[ElZorro]

Interesting stuff as always, Inch.

Ten years does sounds like such a long time, but, all things considered, hopefully, time will fly. I often wonder, though, if these approaches will be "affordable" as treatment options for the general masses or only a fortunate few.

Given the annual cost of HAART, a treatment that costs $100k would be "paid for" in 5 years. The downside is the budgetary process. It's one thing to spend $100k over a span of 5 yrs and another to spend that same $100k in a single year. I continue to hope/pray that when the cure is found, the powers that be will be humane enough to ignore actuarial tables and budgets and "do the right thing" 

[mewithu]

Killing Tcells the good ones, It would take a lot of research before that could become a reality.

[georgep77]

We don't have to wait 10 yrs, tell Dr. Zack I'll be his guinea pig......

            I'll tell the whole world if works.

                                 

[Inchlingblue]

This is just one of the stem cell studies, there are others that are further along.

[veritas]

Inch,

Here another article on new gene therapy hope:

http://www.cbsnews.com/stories/2010/06/18/tech/main6595537.shtml

Here they have already injected the cells in humans. Next phase to see if they can fight the virus.

v

[Inchlingblue]

Inch,

Here another article on new gene therapy hope:

http://www.cbsnews.com/stories/2010/06/18/tech/main6595537.shtml

Here they have already injected the cells in humans. Next phase to see if they can fight the virus.

v

Yes, this is the study that was recently reported on. These were four individuals who have HIV and also had lymphoma. They purposely did not re-infuse that many of the modified HIV-resistant cells back into the patients. They were being cautious in order to see how long the modified cells persisted and if they were safe. Also, these patients had lymphoma so they needed enough non-modified cells to fight the lymphoma.

They found that the modified cells were still present after two years. I believe that it's fully expected that these modified cells will be able to control HIV, it's a matter of re-infusing the right number of them in order to do so.  

The important "proof of concept" here is that the cells persisted after two years and they did not cause any harm. Next time, they will re-infuse much higher quantities of these HIV-resistant cells. The idea is to find the right amount that is safe while also being enough to fight HIV, it's a delicate balance. I hope they are able to open this to clinical trials for people with HIV who do not also have lymphoma.

Once the technology is fine-tuned the idea is to take one's own stem cells, make the appropriate changes on the genetic level that turns them HIV-resistant and then re-infuse them. Essentially re-programming the immune system so that once the new modified cells take hold, HIV is not able to penetrate them.

This is a promising bit from the research:

To make sure that the therapy was safe — and that patients received enough non-engineered cells to treat their lymphoma — Rossi says that the researchers could only include a small proportion of engineered cells in the transplanted mix. That was not enough to reduce the patients' viral load. But the team did see promising hints that the number of engineered cells increased when levels of virus in the blood went up, suggesting that these cells are selected for at the crucial time.

"What we really want to do now is increase the percentage of gene-modified cells in the patient," says Rossi. He and his colleagues are planning a new trial, in collaboration with Benitech, a biotech company based in Melbourne, Australia, in which they will be able to take cell samples containing a larger number of a patient's blood stem cells and transplant only engineered cells, without diluting their effects by also transplanting natural ones.

LINK:

http://www.nature.com/news/2010/100616/full/news.2010.301.html