Eradicating HIV infection, NIH focuses on gene therapy

2024-01-26 06:07:41

February 09, 2018 Source: WuXi PharmaTech

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Case Western Reserve University (CWRU) and Sangamo Therapeutics have announced that they have received a $11 million grant from the National Institutes of Health (NIH) for T cell research in gene editing to eradicate acceptance. Persistent HIV (HIV) infection with antiretroviral therapy.

HIV is a terrible and powerful virus, and although antiretroviral therapy can effectively control viral replication, it does not completely eliminate the virus. This is because HIV-infected cells present in the brain, bone marrow, and reproductive tract are dormant, and they are neither eliminated by antiretroviral therapy nor blocked by the weakened immune system. So if treatment is stopped, the virus begins to replicate and infect more cells, and the immune system cannot suppress this rebound of HIV infection. Therefore, if scientists can find a way to eliminate HIV-infected cells, it may be possible to completely eradicate the virus and make it possible to cure HIV infection.

The grant will fund a clinical trial to test the hypothesis that treatment of patients with their own genetically edited T cells may result in a sustained increase in T cell counts and eradication of latent HIV storage. T cells (because they develop in the thymus) are responsible for various immune responses. Due to the persistence of latent HIV populations, currently available treatments do not completely cure infected individuals. Therefore, if treatment is stopped, the dormant virus will quickly appear and re-infect.

The principal investigator of the new study is Professor Richard J. Fasenmyer of the CWRU School of Medicine and Professor Rafick-Pierre Sekaly, one of the world's leading scientists in the fields of AIDS research, human immunology and immunotherapy. Sangamo Therapeutics will provide materials, equipment and manufacturing expertise for the research, which is expected to begin in 2018.

Sangamo has completed several earlier clinical 1/2 studies to evaluate CCR5-edited T cells (known as SB-728-T) in patients. These one-arm studies (no control group):

It was confirmed that the zinc finger nuclease-driven gene editing effectively knocked out the CCR5 gene in T cells and grows cells in vitro;

A single infusion of SB-728-T is shown to result in T cell implantation and expansion in vivo;

Make long-term persistence of genetically edited cells possible;

A sustained increase in CD4+ T cell counts and significant and sustained attenuation of the HIV reservoir were generated.

No serious adverse events associated with SB-728-T products were found in Sangamo's SB-728-T clinical trial, and no development of anti-zinc finger nuclease antibodies was observed.

The new study was designed to "knock out" the CCR5 gene by T cell from the blood of 20 subjects via zinc finger nuclease gene editing. The CCR5 gene allows HIV to enter host cells. In this process, zinc finger nucleases are engineered proteins similar to genetic "scissors" and are designed to create targeted editing of double-strand break genes in DNA by precise locations determined by the researchers. The newly edited "fixed" cell population will be expanded and reinfused into the patient. The second group of ten patients will receive infusion of unmodified T cells.

â–² Dr. Rafick-Pierre Sekaly, Principal Investigator of the study (Source: CWRU)

Dr. Sekaly said: "For people living with HIV, new treatments can permanently eliminate latent HIV, increase CD4+ T cell counts, and possibly cure infections. This is an important unmet need. Although antiretroviral HIV treatment The standard of care does inhibit viral replication, but HIV infection still exists and patients must continue to receive treatment. And most HIV patients who receive treatment do not have a sustained rebound in T cell counts, leading to chronic increases in inflammation, increased cancer and The risk of other diseases."

Reference materials:

[1] Case Western Reserve and Sangamo Therapeutics Announce $11M NIH Grant for Study of Gene-Edited T Cells for Viral Eradication of HIV

[2] Sangamo Therapeutics official website

Insufflator

ZHEJIANG SHENDASIAO MEDICAL INSTRUMENT CO.,LTD. , https://www.sdsmedtools.com