Novel stem-cell transplants could be an HIV cure

BioTechniques News
Aisha Al-Janabi

The first female, nonwhite and HIV-positive cancer patient treated with a new stem-cell transplant therapy is now in long-term remission – suggesting that transplanting umbilical cord blood with the CCR5Δ32 gene variant offers a potential HIV cure.

A new case of long-term HIV remission was reported on February 15th 2022, at the 29th annual Conference on Retroviruses and Opportunistic Infections, in Denver (CO, USA). The announcement originates from an NIH-funded clinical trial at Weill Cornell Medicine (NY, USA) led by stem-cell transplant specialists Jingmei Hsu and Koen Van Besien, and infectious-disease specialist Marshall Glesby (all from Weill Cornell Medicine). This was also in collaboration with researchers at the University of California, Los Angeles (LA, USA), Johns Hopkins University (MD, USA), and several other institutions. The cancer patient, who was also living with HIV, received a blood stem-cell transplant for high-risk acute myeloid leukemia and has since been free of the virus for 14 months, and no longer requires HIV antiretroviral drug treatment.

Initially, the patient received high-dose chemotherapy to destroy her own blood- and immune-cell populations. This was followed by a novel blood- and immune-cell transplantation procedure from two sources: stem cells from a healthy adult relative of the patient were used to rapidly restore her blood cell population to prevent the risk of infection, and umbilical cord blood from an unrelated child was transplanted to provide long-term blood reconstitution. The cord blood contained an HIV-resistance gene variant called CCR5Δ32, which is important for blocking viral entry to immune cells via the CCR5 co-receptor.

How does the immune system self-regulate?

Researchers have been studying regulatory T cells – named Tregs – and discovered that they control our immune response in two different waves.

There have been two prior cases of long-term remission in HIV-positive cancer patients after adult CCR5Δ32 stem-cell transplantation; however, this is the first case to use cord blood cells. This study is also a pioneer in HIV treatment as it is the first to treat a woman and someone who identifies as mixed-race. Traditionally, it has been difficult to find suitable adult stem-cell donors for transplants in nonwhite patients since the CCR5Δ32 variant is more common in people of European heritage. The use of cord blood partly alleviates this difficulty, and may pave the way for more stem-cell transplantations in nonwhite HIV-positive cancer patients.

Post-transplant studies 3 months later, revealed that the patients’ blood cell population was entirely derived from the HIV-resistant umbilical cord blood cells and that HIV was no longer detectable. This enabled the patient to eventually stop taking the antiretroviral drugs and has remained free of HIV re-emergence for the 14 months since. This likely indicates a cure; however, the research group prefers to refer to the patients’ current condition as long-term remission at this stage. After this stem-cell transplant, the patient has also remained leukemia-free for more than 4 years.

The team is confident that cord blood containing the CCR5Δ32 variant is a potential cure for both hematological malignancies (cancers that primarily affect blood-forming tissue) and HIV, and as such should be considered as a stem-cell source when HIV-positive cancer patients require blood stem-cell transplants. However, the procedure is currently deemed too dangerous for HIV-positive patients who are not already in need of such transplants.

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