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As part of a major breakthrough in the fight against cancer, UCLA scientists show they are able to generate and develop mature T-cells with crucial receptors for cancer control from cells pluripotent strains. In addition, these stem cells do not necessarily have to come from the cancer patient, which paves the way for a ground-breaking, affordable and effective off-the-shelf immunotherapies avenue for cancer patients.
Using stem cells to build battle-ready T cells
In a recent study, published in the journal Cell strain cell, Gay Crooks, professor of pathology and laboratory and pediatric medicine at UCLA, along with co-author Amélie Montel-Hagen, badociate research fellow at Crook's laboratory, and Dr. Christopher Seet, clinical instructor at the division of Hematology oncology at UCLA, shows for the first time how pluripotent stem cells could be used to generate stronger, more mature T cells able to fight and kill cancer cells.
The specificity of pluripotent stem cells lies in the fact that they are stem cells that can be induced to produce any type of cells in the human body. Most importantly, in this case, they can also be grown without limit in the laboratory, which means that the number of pluripotent stem cells that scientists can use to create T cells provides the possibility of an unlimited supply of lymphocytes T for the future immunotherapies.
Why are T cells so promising in the fight against diseases like cancer
T cells are the cells of our body that the immune system uses to fight infections, but that have also shown promise to eliminate cancer cells. Current T-cell therapies typically involve taking a sample of the patient's own T cells, genetically modifying the cells with a receptor capable of detecting and fighting cancer cells as if it were a tumor. An infection, and then reinject them back to the patient.
The problem is that genetically modified T cells can malfunction and are therefore not effective anticancer agents. The treatments are also usually very expensive because they are tailored to each patient (he must use the patient's own T cells), which may not be possible with some cancer patients with too few T cells.
This is a treatment that can produce T cells that do not rely solely on the patient getting them to create affordable and effective treatments accessible to more people.
Replicate body design in the laboratory
Members of the Crooks team are not the first to attempt to generate T cells from pluripotent stem cells, but previous efforts have had limited success and no fully developed T cells mature and functional, even when combined with a layer of support cells. .
Crooks and his team took a different approach. They used 3D structures called artificial thymic organoids to simulate the thymus, the organ responsible for transforming blood stem cells into T cells.
Having previously shown that artificial thymic organoids could be used to generate mature T cells from blood stem cells, the team felt that it was also possible to do the same using pluripotent stem cells .
"What's exciting is that we start with pluripotent stem cells," says Crooks. "I hope this technique will look to the future. We can combine it with the use of gene editing tools to create standard T's. " cell therapies more easily accessible to patients. "
Their study showed that thymic artificial organoids were in fact able to produce mature T cells from two different forms of pluripotent stem cells currently used in laboratory research: embryonic stem cells, produced from donated embryos, and induced pluripotent stem cells. , produced by reprogramming the skin or adult blood cells to return to a form similar to that of their initial embryonic state.
In addition, their study showed that they could make these stem cells express a receptor specific for anti-cancer T cells, which would give T cells that they would produce the ability to search for and destroy tumor cells at home. the mouse.
By using genetic engineering techniques, these T cells could even be adapted to the fight against certain forms of cancer. "Once we have created genetically modified pluripotent stem cell lines that are able to produce tumor-specific T cells in artificial thymic organoids," says Montel-Hagen, "we can develop these stem cell lines indefinitely."
Challenges remain
One of the remaining problems for the team is that, since T cells are not collected directly from patients, T cells produced with artificial thymic organoids contain additional surface molecules that could themselves trigger immune responses of patients, resulting in the T lymphocytes are rejected and destroyed by the body of the patient.
"Our next step, according to Seet, will be to create T cells with receptors to fight cancer, but not molecules responsible for cell rejection, which would be a major step towards the development of universal T. cellular therapies. "
There is also a long way to go before this technique can be used by patients seeking immunotherapy treatment for their cancer. Until now, the artificial thymic organoid technique has only been used in mice and is not yet available for clinical trials, any more than FDA-approved T cells produced by artificial thymic organoids for use in humans.
Opportunities beyond cancer treatments
While the study focused specifically on cancer cells, the Crooks team's ability to generate functional T lymphocytes from an artificial thymic organoid expressing specific receptors could change the game for other diseases than cancer. .
Since T cells also fight bacterial and viral infections, the potential applications in the treatment of infections such as HIV or antibiotic-resistant bacteria are just as promising. Their effectiveness in these other areas remains to be determined, but the outlook is positive.
A T lymphocyte is a T lymphocyte, whether it is the fight against cancer or the common cold, future therapies based on the work of Crooks, Montel-Hagen and Seet are very promising. And with the increase in the number of antibiotic-resistant bacteria, new treatments for diseases could not happen too soon.
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