Treatment strategy developed by Einstein may lead to cure of HIV and other chronic viral infections
Proteins designed to concentrate the immune attack on cells infected with HIV.
Armed with a new strategy they developed to boost the body’s immune response, scientists at the Albert Einstein College of Medicine were able to suppress HIV infections in mice, providing a path to a working cure for HIV and other chronic viral infections. Their findings were published on October 21, 2021 in the Clinical investigation journal.
The research involved proteins designed to selectively stimulate CD8 + “killer” T cells of the immune system to multiply and specifically attack T cells infected with HIV. Co-correspondent author Steven Almo, Ph.D., developed the synthetic proteins, known as synTac (short for “synapse for T-cell activation”). Dr Almo is Professor and Chairman of Biochemistry, Professor of Physiology and Biophysics, Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology, and Director of the Macromolecular Therapeutics Development Facility at Albert Einstein College of Medicine.
HIV infects CD4 + T cells of the immune system. Over the past 25 years, people with HIV have been able to control their infection with antiretroviral therapy (ART), a combination of several drugs that prevent HIV from infecting new CD4 + T cells and multiplying in them. breast. “While ART works remarkably well in controlling HIV indefinitely, it is a dead end, not a checkmate,” said co-correspondent author Harris Goldstein, MD, professor of pediatrics and of Microbiology and Immunology and Charles Michael Chair in Autoimmune Diseases at Albert Einstein College of Medicine and Director of the Einstein-Rockefeller-CUNY Center for AIDS Research.
“Long-term use of ART can cause significant side effects,” noted Dr. Goldstein. “And once ART is stopped, latent HIV viruses, which can persist for years in CD4 + T cells, invariably come out of their hiding places to rekindle the infection. Our JCI The article shows that the synTac proteins, by considerably increasing the quantity of protective CD8 + T cells specific for HIV, were able to eliminate these infected cells.
“It is unlikely that a treatment strategy could eliminate all latently infected T cells,” said Dr Goldstein. “Our goal with synTac is a ‘working cure’, in which the potent immune response induced by synTac suppresses HIV to levels undetectable even after stopping ART.”
The researchers first tested their anti-HIV synTac proteins on human blood samples infected with HIV or cytomegalovirus (CMV), a common type of herpes virus that can infect and kill immunocompromised patients. For blood from human donors infected with HIV or CMV, specific synTacs to mobilize immune responses against these viruses triggered selective and vigorous multiplication of CD8 + T cells which exhibited potent HIV or CMV antiviral activity.
Next, the researchers injected HIV-specific or CMV-specific synTacs intravenously into mice infected with the virus with a “humanized” immune system that allows infection with viruses affecting people, such as HIV and AIDS. CMV. The synTac proteins triggered a 32-fold increase in human CD8 + T cells specific for HIV and a 46-fold increase in human CD8 + T cells specific for CMV. In mice infected with HIV and CMV, the large number of human CD8 + T cells stimulated by synTac strongly suppressed viral infections, suggesting that synTacs may offer new opportunities to functionally heal HIV and treat CMV and other viral infections.
“A key advantage of the synTac platform,” said Dr. Almo, “is the ease with which we can program synTac proteins to fight one of the many diseases in which T cells play a role, including disease targets that extend far beyond viruses. For example, an ongoing clinical trial involving patients with head and neck cancer is evaluating the ability of synTac to selectively activate anti-cancer T cells. And because synTacs can turn off and turn on T cells, they’re also being studied to treat type 1 diabetes and other autoimmune diseases by turning off T cells that mistakenly attack healthy tissue in people. Dr Almo is also co-head of the cancer treatment program at the Albert Einstein Cancer Center.
Reference: “T-Cell Receptor-specific Immunotherapeutics Drive Selective In vivo HIV and CMV-specific T-Cell Expansion in Humanized Mices” by Mengyan Li, Scott J. Garforth, Kaitlyn E. O’Connor, Hang Su, Danica M. Lee , Alev Celikgil, Rodolfo J. Chaparro, Ronald D. Seidel, R. Brad Jones, Ravit Arav-Boger, Steven C. Almo and Harris Goldstein, October 21, 2021, Clinical investigation journal.
DOI: 10.1172 / JCI141051
Other authors involved in the research were Ph.D. student Mengyan Li, Scott J. Garforth, Ph.D., Kaitlyn E. O’Connor, Hang Su, Ph.D., Danica Lee and Alev Celikgil, MD , all from Einstein; Rodolfo J. Chaparro, Ph.D., and Ronald Seidel, Ph.D., of Cue Biopharma; R. Brad Jones, Ph.D., of Weill Cornell Medical College in New York; and Ravit Arav-Boger, MD, of the Medical College of Wisconsin.
The underlying synTac technology, also known as Immuno-STAT ™ from Cue Biopharma (Selective targeting and alteration of T cells) platform, was developed in the laboratory of Dr. Almo. It is patent protected and licensed to Cue Biopharma, of which Dr Almo, Dr Seidel and Dr Chaparro are co-founders and shareholders. Einstein received financial support from Cue Biopharma for previous studies. Einstein’s HIV application (US Application: 16/603306) is patent pending and the College of Medicine is currently seeking help to further its development.
About the Albert Einstein College of Medicine
The Albert Einstein College of Medicine is one of the country’s leading centers for research, medical education and clinical investigation. In the 2020-21 academic year, Einstein welcomes 721 medical students, 178 doctoral students. students, 109 students in the combined MD / Ph.D program. program and 265 postdoctoral fellows. The College of Medicine has over 1,900 full-time faculty members located on the main campus and in its clinical branches. In 2020, Einstein received more than $ 197 million in awards from the National Institutes of Health (NIH). This includes funding for Einstein’s leading research centers in aging, intellectual developmental disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is focusing its efforts include research in brain development, neuroscience, heart disease, and initiatives to reduce and eliminate ethnic and racial disparities in health. Its partnership with Montefiore, the University Hospital and Einstein University Medical Center, advances clinical and translational research to accelerate the rate at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and training programs in the medical and dental professions in the United States through Montefiore and an affiliate network involving hospitals and medical centers in the Bronx, Brooklyn and Long Island.