April 13, 2012
Engineering CD8 Cells to Kill HIV in Tissues
by Trenton Straube
Expanding on previous research providing proof-of-concept that human stem cells can be genetically engineered into HIV-fighting cells, researchers at the University of California at Los Angeles (UCLA) have now demonstrated that these cells can actually attack HIV-infected cells in a living organism.
The study, published April 12 in the journal PLoS Pathogens and highlighted in an accompanying news announcement, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model.
“We believe that this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body,” said Scott Kitchen, PhD, of the David Geffen School of Medicine at UCLA and an author of the PLoS Pathogens report, according to an accompanying news announcement.
In the previous research, the scientists took CD8 cytotoxic T lymphocytes—the “killer” T cells that help fight infection—from a person living with HIV and identified the molecule known as the T cell receptor, which guides the T cell in recognizing and killing HIV-infected cells.
While these cells are able to destroy HIV-infected cells, they do not exist in great enough quantities to clear the virus from the body. So the scientists cloned the T cell receptor and used this to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.
The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.
In this current study, Kitchen and his colleagues similarly engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates. They did so by using a surrogate model—the humanized mouse—in which HIV infection closely resembles the disease and its progression in humans.
In a series of tests on the mice’s peripheral blood, plasma and organs conducted two weeks and six weeks after introducing the engineered cells, the researchers found that the number of CD4 cells increased, while viral load decreased.
The researchers did note a potential weakness with the study: Human immune cells reconstituted at a lower level in the humanized mice than they would in humans, and as a result, the mice’s immune systems were mostly, though not completely, reconstructed. Because of this, HIV may be slower to mutate in the mice than in human hosts. So the use of multiple engineered T cell receptors may be one way to adjust for the higher potential for HIV mutation in humans.
“We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people,” Kitchen said.
Next up, Kitchen and his colleagues say they will begin making T cell receptors that target different parts of HIV and that could be used in more genetically matched individuals.
Search: cd8, cd4, t cells, cytotoxic t lymphocytes, ucla, stem cells, genetic engineering, kitchen, plos
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comments 1 - 15 (of 30 total) next
randall ralston, keller, texas, 2013-03-10 03:23:07
hi, with n open mind i noted that the results in mice humans are different because of hiv mutatiion rates, but what if the solution lied in the glycoprotein amounts or glucose levels insted of the focus of how fast the RNA take to switch to dna n mutate the host cell.hiv mask itself by tricking the cell into thinking its sugar basiclly. so have we taken in to consideration of the suger levels of the host and how much that host may produce.are mutation rates veryied in each host.thx
D. Elijah Vanlue Jr., Philadelphia, PA, 2012-07-25 05:37:52
i noticed that it said that the cells would need to be a match in order to be transplanted... um, have they thought about trying to salvage healthy cells they can extract to build models from in order to expedite the matching process... this is exciting and i'm sure that there are plenty of folks who already ready to jump on the bandwagon for human trials...as evidenced by many of the comments here...
MAT STRAZZ, boston MA USA, 2012-07-03 17:08:58
I feel that we need a new push, to get to the new treatment, to get to a cure. It is about time that billions of dollars are pored into research. Finding the cure for hiv will mean finding the cure for many other diseases. The future cost of doing nothing is so massive that it will eat up our healthcare and the healthcare of the world. The world must now make the final push to devolop a cure that can be replicated and used world wide. we can not let the problem get much bigger.
Douglas, Ventura, 2012-05-25 23:17:53
Excellent news would like to know when human trials begin. Thank You
Matt, Toronto, 2012-05-22 21:10:11
My question is would this also work on herpes? Obviously HIV is the more life threatening problem, but herpes is a very common disease too. With similar problems with it hiding and even going dormant.
barbara, santa fe, 2012-05-17 12:33:26
I a person that got hiv from working in surgery..i would love to be a canidate for trials.
Rick, Sioux City, 2012-05-15 16:13:14
When will tests be run on humans. I would love to be a volunteer.
William, Sarasota, 2012-05-10 10:56:46
My biggest concern would be the life span of the modified CD-8 cell. Do they replicate.
How would the treatment work if someone was infected with different versions of the virus.
Modified CD-8 would probably work best on the newly infected.
keith, Dublin, 2012-05-04 18:09:12
I have noticed a slight problem and obstacle in all this cure research and that is "what is a cure". They seem reluctant to declare people as cured even if off ARVs for 2-10 yrs .
The problem is of course the fact that HIV can be passed between people. Will a government ever declare a once HIV+ person HIV-.
There has to be an agreement made of when a person is cured .
When in tests will they declare someone HIV-
What will be the criteria for a sterilizing or functional cure. They need to decide.
cathy, ashtabula,ohio, 2012-04-30 14:48:39
Please, i'd love to know where to sign up for this. I'm game!!! Thank you!!!
lifeIsBeautiful, UK, 2012-04-30 14:11:16
All the research with regard to the CURE flarred up after 'The Berlin Patient'. Timothy's case proved that HIV can be removed from the body resulting in funding for cure which otherwise was sidelined. If you guys want to know more about the progression of these research you can visit the following site 'clinicaltrials.gov'
Its a registry that holds data of all the clinical trials going in the world. search for 'ZFN' and you will see where the progress is.
tupac, Durban south africa, 2012-04-30 09:32:38
Well done to the research team.May our LORD grant you all the necessary knowledge to find a complete cure using stem cell research.I would love to be your "guinea pig".
GOD SPEED ! Tupac
Ranjan, India, 2012-04-30 06:22:23
My hope is the introduction of a one shot treatment which holds good for say 6 months to an year which can stop the replication and activation of virus with no need for the daily dose of medication which have serious side effects. Such a development will be such a boon till a cure is developed.
JM, Colorado, 2012-04-29 17:43:43
I would give my life for research and a cure for this. From a person who has lived with this and knows numerous others who hv lived and pasted with this. Where can i sign up.
Samahamba Kadyochi, Lusaka, 2012-04-26 13:37:33
comments 1 - 15 (of 30 total) next
Excellent news; one day the correct combinations will come together for a cure and what a day it shall be. Please keep feeding the HOPE.
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