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New CAR-T Therapy Inhibits HIV Infection New CAR-T Therapy Inhibits HIV Infection

In 2017, FDA approved the first gene therapy for cancer - CAR-T therapy. Recently, scientists reported that the same genetic engineering cell technology has shown to inhibit HIV infection in laboratory animals and may even eradicate HIV. Although the study was very small, the genetic engineering "CAR" cells were tested on only two leprosy and laboratory-grown cells, but the results suggest that after 30 years of hard work to develop an AIDS vaccine , People may have new ways to help the immune system fight HIV infection.

Dr. Bruce Walker, MIT and Harvard University's MGH Ragon Research Institute, said: "This study shows that in animal models, stem cells can be engineered to respond to HIV-infected cells using immune system targets An impressive first step towards HIV. "Dr. Walker pioneered ground-breaking genetic engineering of immune cells to fight HIV in the 1990s, but he was not involved in the new study. He said: "Although the current effect is not entirely satisfactory, it obviously gave us some constructive things to further development."

To engineer T cells to fight cancer, scientists have given T cells genes that recognize surface molecules on tumor cells that bind tumor cells, called chimeric antigen receptors or CARs. Binding of the antigen to the receptor activates CAR-T cells, causing them to kill the tumor cells.

Instead of genetically modifying T cells themselves, scientists in the study genetically engineered stem cells that produce T and other blood cells, hematopoietic stem cells, to create HIV-positive T cells. This modification provides an HIV-specific CAR for hematopoietic stem cells and all their offspring. Part of this CAR, called CD4, hunts for and binds to HIV, while another surface molecule, called C46, blocks HIV from entering T cells. This allows T cells to detect the virus without infecting the virus. In addition, such T cells can also find and destroy HIV-infected cells because these cells have some of the same T-cell-attracting surface molecules as HIV.

Genetically engineered T cells not only destroyed HIV-infected cells in both flat-capped monkeys and in cell culture experiments, but the effect lasted for more than two years. This shows that they can "provide lasting anti-HIV capacity." "The authors believe that stem cell methods have greater potential for long-term suppression of the HIV virus, and even, said Dr. Scott Kitchen, an immunologist at the University of California, Los Angeles, at the University of California, Los Angeles, in a study published in the journal" PloS Pathogens. Eradicate the virus. "

Dr. Kitchen said it is likely to begin clinical trials in two years and he is discussing with private gene therapy company Calimmune and others how to develop the method. "Genetically engineered stem cells will initially be an expensive method, but it is possible to avoid the necessity and expense of taking antiretroviral drugs for life," Dr. Cook added. He and his colleagues are working to develop genetically engineered cells into vaccines, which may lower their prices.

Another reason to be cautious aside from the price is that CAR-T's anti-HIV attempt has failed before. The basic idea of genetic engineering immune cells anti-HIV can be traced back to at least 1997. A team led by Dr Walker at the time found that a CAR-T cell could destroy HIV in laboratory-grown cells. But when scientists tested the method on a small number of patients, the results were disappointing. This may be because the CAR-T cells were killed by the virus before they could kill the virus.

Dr. Kitchen said creating CAR stem cells instead of CAR-T might solve the problem. Genetically engineered hematopoietic stem cells are capable of "providing an unlimited supply of engineered T cells that can continue to attack HIV," just as an army with countless alternative soldiers.

The therapy has the effect of inhibiting HIV infection (Source:
▲ The therapy has the effect of inhibiting HIV infection (Source: "PloS Pathogens")

Their experimental results in leprosy confirmed this. In the experiment, two leprous monkeys received genetically engineered stem cell transplantation; the other two received inactive gene-modified stem cells as controls. Experimental results show that transplanted stem cells can enter the bone marrow and produce HIV-CAR-T for two years. No adverse effects were observed in animals and CAR-T killed the infected cells. However, the effect of reducing the number of viruses in animals is less than optimal.

In addition, they found that these killer cells can enter the sites where HIV most often replicates, including the lymphatic system and the gastrointestinal tract. Dr Walker said it was "impressive" because it raised the possibility that CAR-Ts cleared AIDS from hidden parts of the body.

Genetically engineered cell therapies are rapidly evolving, and we look forward to more effective treatments to alleviate the suffering of AIDS patients.
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