Stem cell transplant could cure HIV
summary: Researchers found that two non-human primates were cured of the simian HIV simian immunodeficiency virus (SIV) after stem cell transplantation.
The researchers tracked the order in which HIV is cleared from the body by identifying two conditions that must be matched for healing to occur. This insight could help develop a broader treatment for HIV, which affects about 38 million people worldwide.
Ultimately, scientists hope to make the treatment more accessible, ideally in a single injection, rather than requiring a stem cell transplant.
- The study matched five known cases of HIV cured by stem cell transplantation and found that successful stem cell transplantation may cure HIV.
- The researchers found that for healing, the transplanted donor stem cells must kill the recipient’s HIV-infected cells, preventing HIV from using the CCR5 receptor to infect the donor cells.
- The research team also documented the gradual manner in which HIV is cleared from the body, starting with blood circulating in the extremities and continuing through lymph nodes in the extremities and abdomen.
sauce: Oregon Health & Science University
A new study from Oregon Health and Science University helps explain why at least five people have been freed from HIV infection after receiving a stem cell transplant.
The study’s insights could bring scientists closer to developing what is hoped to be a broader treatment for the virus that causes AIDS, which infects about 38 million people worldwide.
Published in today’s magazine immunity, an OHSU-led study describes how two non-human primates were cured of simian HIV after undergoing stem cell transplantation. He also reveals that two conditions must coexist for treatment to occur, documenting the order in which HIV is cleared from the body. This detail can inform efforts to make this treatment available to more people.
“Five patients have already proven that HIV can be cured,” said lead investigator of the study, Dr. Jonah Sasha, professor at OHSU’s Oregon National Primate Research Center and Institute for Vaccines and Gene Therapy. Stated.
“This study will help us understand the mechanisms that enable that therapy,” Sacha continued. “We hope our findings will help make this treatment work for everyone, ideally with a single injection rather than an injection.” stem cell transplant”
The first known case of HIV cured by stem cell transplantation was reported in 2009. A man who had lived with HIV was also diagnosed with acute myeloid leukemia, a form of cancer, and underwent a stem cell transplant in Berlin, Germany. Stem cell transplantation, also called bone marrow transplantation, is used to treat some cancers.
Known as the Berlin patient, he received stem cells from someone with a mutated CCR5 gene that encodes a receptor on white blood cells that HIV normally uses to infect new cells.
Mutations in CCR5 make it difficult for the virus to infect cells and may make people resistant to HIV. Since the Berlin patient, four more have been similarly cured.
The study was conducted using a non-human primate species known as the Mauritian cynomolgus monkey, which the research team previously demonstrated to be successful in stem cell transplantation.
All eight study subjects were HIV-infected, four of whom received stem cell transplants from HIV-negative donors, and the other half who did not receive transplants as study controls.
Two of the four transplant recipients were successfully treated for graft-versus-host disease commonly associated with stem cell transplantation and were cured of HIV.
Other researchers have used similar methods to cure HIV infection in nonhuman primates, but this is the first time that a research animal cured of HIV has survived for a long time.
Nearly four years after the transplant, both are alive and HIV-free. Dr. Sasha said they survived because of the exceptional care by veterinarians at the Oregon National Primate Research Center and study co-author Richard, two OHSU clinicians in charge of caring for people undergoing stem cell transplants. It credits the support of T. Magiartz, M.D., and Gabriel Myers, M.D.
“These results highlight the power to combine clinical studies in humans with preclinical experiments in macaques to answer questions that would otherwise be impossible, and provide avenues for curing human disease. ,” said Maziartz, a professor of medicine. He is Professor of Medicine at the OHSU School of Medicine and Medical Director of the Adult Blood and Bone Marrow Stem Cell Transplant and Cell Therapy Program at the OHSU Knight Cancer Institute.
behind the treatment
Sacha said he was happy to confirm that stem-cell transplantation cured non-human primates, but he and his fellow scientists also wanted to understand how it worked. When evaluating samples taken from subjects, scientists discovered that he had two ways of beating HIV.
First, the transplanted donor stem cells helped kill the recipient’s HIV-infected cells by recognizing them as foreign invaders and attacking them. This is similar to the graft-versus-leukemia process that cures cancer in people.
Second, in the two subjects who did not heal, the virus was able to enter the transplanted donor cells. Subsequent experiments confirmed that HIV can infect donor cells while they are attacking HIV. This led researchers to conclude that preventing HIV from using the CCR5 receptor to infect donor cells was also necessary for cure.
Researchers also found that HIV is cleared from the subject’s body in a series of steps. First, scientists confirmed that HIV was no longer detected in the blood circulating in the arms and legs.
Second, they couldn’t find HIV in the lymph nodes, the clumps of immune tissue that contain white blood cells and fight infection. HIV infection was first detected in extremity lymph nodes, followed by abdominal lymph nodes.
The step-wise manner in which scientists have observed HIV elimination may help doctors evaluate the effectiveness of potential HIV treatments. For example, clinicians can focus on analyzing blood collected from both peripheral veins and lymph nodes.
This knowledge may also help explain why some transplant recipients initially appeared cured but were later found to have HIV. Sascha hypothesizes that these patients may have small reservoirs of HIV in their abdominal lymph nodes, allowing the virus to persist and spread again throughout the body.
Sasha and colleagues continue to study two non-human primates who have been cured of HIV. We will then investigate the immune response in greater depth, including identifying all the specific immune cells involved and identifying which specific cells or molecules were targeted by the immune system.
Funding: This work was supported by the National Institutes of Health (grant AI112433, AI129703, P51 OD011092), the AIDS Research Foundation (grant 108832), and the AIDS Immunity Research Foundation. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
To ensure the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages any relationships our researchers may have with bodies outside OHSU. I’m here.
Regarding this research, Dr. Sacha has a significant financial interest in CytoDyn, which may have commercial interest in the research results and technology. Learn more about OHSU’s Conflict of Interest Program to learn how we manage these business relationships.
All research involving animal subjects at OHSU must be reviewed and approved by the university’s Animal Care and Use Committee (IACUC). The priority of IACUC is to ensure the health and safety of animal research subjects. The IACUC will also review procedures to ensure the health and safety of those who work with animals. OHSU cannot work on live animals without IACUC approval.
About this stem cell research news
author: Franny White
sauce: Oregon Health & Science University
contact: Franny White – Oregon Health & Science University
image: Image credited to Neuroscience News
Original research: closed access.
“Alloimmunization clears latent virus after allogeneic stem cell transplantation in SIV-infected antiretroviral therapy-suppressed macaque monkeysby Jonah Sasha et al. immunity
Alloimmunization clears latent virus after allogeneic stem cell transplantation in SIV-infected antiretroviral therapy-suppressed macaque monkeys
- Elimination of the SIV reservoir by alloimmunization after allogeneic stem cell transplantation
- Clearance of SIV reservoirs after transplantation occurs in stages, first with blood and then with tissue.
- CCR5+ allogeneic HSCT can functionally cure macaque monkeys with SIV
- Despite complete suppressive therapy, SIV spreads to engrafted CCR5+ donor cells
Allogeneic hematopoietic stem cell transplantation (alloHSCT) from a donor lacking CC chemokine receptor 5 (CCR5)D32/D32) can treat HIV, but the mechanism remains speculative.
To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV.+, antiretroviral therapy (ART) suppresses the Mauritian cynomolgus monkey (MCM), and alloimmunity is the major factor in reservoir clearance, first in the peripheral blood, then in the peripheral lymph nodes, and finally in the gut flowing through the gastrointestinal tract. It has been demonstrated to occur in mesenteric lymph nodes. .
Alloimmunization may eradicate latent viral reservoirs and did so in two allogeneic HSCT recipient MCMs who maintained viremia >2.5 years after cessation of ART, but in other cases, due to CCR5 tropism , was inadequate without the protection of engrafting cells conferred by CCR5 deficiency.Virus spreads to donor CD4+ T cells despite complete suppression of ART.
These data demonstrate the distinct contributions of alloimmunity and CCR5 deficiency to HIV cure and support the definition of targets for alloimmunity in therapeutic strategies independent of HSCT.
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