Hello Dr. @ThomasTu @availlant @john.tavis
I just came across this article dated 1/11/2024 and was wondering if you have heard of it ( it’s from San Raffaelle hospital in Milan) the scientists involved are Dr. Matteo Iannacone and Dr. Luca Guidotti. I understand its a preclinical model but it sounds promising.
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For the first time in the world, an immunotherapy capable of combating chronic hepatitis B has been tested on preclinical models
01/11/2024
Immunotherapy could also prove to be an effective solution for the treatment of chronic hepatitis B, which afflicts over 300 million people worldwide and is among the primary risk factors for liver cirrhosis and liver cancer. In fact, it seems that interleukin-2 (Il2) is able to reactivate the immune system of the HBV virus infection, which normally becomes chronic precisely because the body’s defenses are unable to eradicate the virus, which continues to survive and reproduce. inside the liver cells.
The first tests in the world on the molecule were conducted on preclinical models by a group of researchers from the Irccs San Raffaele hospital in Milan and the Vita-Salute San Raffaele university, in collaboration with the American start-up Asher Biotherapeutics. The results are published in Science Translational Medicine.
Existing therapies
The hepatitis B virus – they recall from San Raffaele – is transmitted by contact with infected blood, sexually or from mother to child during childbirth. Unlike what happens when an adult contracts the virus, over 90% of children infected at birth develop the chronic form of hepatitis B. Today there is a preventive vaccine against the infection, but patients who have already contracted it do not have it can benefit.
The turning point
For them, a possible turning point comes from the study coordinated by Matteo Iannacone, director of the Division of Immunology, Transplants and Infectious Diseases of the Irccs San Raffaele hospital, who returned to Italy after a long experience in the United States thanks to the Career Development Award of the Armenise-Harvard Foundation . Iannacone’s research, in synergy with the unit directed by Luca Guidotti, deputy scientific director of San Raffaele, has contributed in recent years to developing some of the antivirals commonly used to treat hepatitis B in its chronic form.
Previous research
Already in 2019, with some data published in Nature, through a molecular analysis carried out thanks to intravital microscopy techniques, scholars had demonstrated that T lymphocytes are unable to eradicate Hbv infection and are dysfunctional since their activation. The characterization of dysfunctional T lymphocytes had also allowed the San Raffaele researchers to identify the most suitable and effective molecules for reawakening these cells.
The role of IL2
One is interleukin-2, a messenger molecule of the immune system, which acts as a sort of immunotherapy and has already been successfully tested both in cultured cells obtained from patient samples and in animal models. However, Il-2, when administered systemically, produces serious side effects, increasing the permeability of blood vessels and causing severe edema. This happens because the molecule not only acts on T lymphocytes, but also on Natural killer cells that induce toxicity, as well as on regulatory cells that inhibit the immune response. The new study bypasses these obstacles.
“cis-targeting”
The results just published in the journal Science Translational Medicine add a piece to those published in 2019. Thanks to the collaboration with the company Asher Biotherapeutics which produces interleukin-2, the researchers managed to experiment with this molecule, developing an approach called " cis-targeting”. That is, interleukin-2, conjugated with a specific antibody, is able to target only T lymphocytes, activating them correctly against the disease.
Open road to immunotherapy
“We have seen in mouse models of the disease that, by administering this type of immunotherapy, the T lymphocytes expand in number and increase their function, i.e. they release cytokines capable of inhibiting viral replication and eliminate the infected cells, effectively killing the virus ”, comments Iannacone.
The results have therefore demonstrated, in preclinical models of hepatitis B and in the blood of healthy people, the safety, low toxicity and therapeutic efficacy of this innovative approach. “In addition to antiviral approaches, it is possible to finally think about an immunotherapy strategy. The next step is to test this approach on humans, in combination with antivirals,” concludes the researcher.
The research was supported by the European Research Council (ERC), the Airc Foundation for cancer research, the Ministry of Health and the Ministry of University and Research.
Source: aboutpharma.com