Chronic hepatitis B, stimulate the immune system to eliminate the virus

Chronic hepatitis B, stimulate the immune system to eliminate the virus

The latest promise of immunotherapy targets hepatitis B. It comes from a team of researchers at the IRCCS San Raffaele Hospital in Milan and aims to help achieve what so far neither the vaccine, although quite effective, nor antivirals, they managed to do: eradicate the hepatitis B virus from the body.

The challenge against chronic hepatitis B infections

Hepatitis B is a disease of viral origin that can occur in acute and chronic form. The acute form, more typical of adulthood, lasts a few weeks and can generally be eradicated, unlike the chronic one. In the latter case, it is estimated that the infection occurs in children in 90% of patients.

Against chronic infection the vaccine – although very effective – does not work (also because it is a prevention tool) and the only option for patients is to rely on antivirals, as he recalls Matteo Iannacone, Director of the Division of Immunology, Transplants and Infectious Diseases of the IRCCS San Raffaele Hospital and Professor of General Pathology at the Vita-Salute San Raffaele University, head of the study on the promises of immunotherapy against hepatitis B: “Antivirals inhibit replication of the virus but they are unable to eradicate it and must be taken for life, without completely eliminating the risk of developing cirrhosis and liver cancer”. A real risk for the approximately 300 million people who currently live with the virus.

Unlike what happens in hepatitis C – where antivirals have represented a real revolution in medicine, thanks to which it is possible to eradicate the virus within a few weeks – the hepatitis B virus is able to hide better inside of the cells, Iannacone continues: “The hepatitis B virus is a DNA virus, it integrates into the genome and in any case persists in the nucleus, and this makes its eradication more difficult”.

Immunotherapy to awaken T lymphocytes against the virus

The idea is that alongside new antivirals, capable of reaching places where the current ones do not reach, something else is also needed. Maybe something capable of mimicking the immune system’s response in the case of acute infection. “In the acute form our immune system is able to defeat the virus, in the chronic form it is not, and this is because the cells responsible for doing so are dysfunctional, they are so to speak turned off, asleep”. A situation, explains the expert, which occurs when the antigen (in this case the virus, ed.) persists within the body and which has evolved to avoid excessive activation of the immune system: “Our idea is was to find a way to reawaken these T lymphocytes, thanks to immunotherapy”. To do this, the researchers decided to use interleukin-2, a cytokine capable of acting on T lymphocytes, but not only on them. The result is that if “unguided” it can be toxic or even repress the immune response, the experts explain. Hence the idea of ​​ferrying it only where it is needed, to the cytotoxic T lymphocytes, capable of eliminating the infected cells.

Eradicating the virus, successful trials (in mice)

To do this, the researchers, in collaboration with the start-up Asher Biotherapeutics, used a construct in which interleukin-2 is attached to an antibody specific for these T lymphocytes, so as to spare other cell populations. Tested on preclinical disease models, such as mice, the researchers say pages Of Science Translational Medicine, the molecule works. That is, it manages to expand and activate the populations of T lymphocytes against the virus, breaking down the viral load and antigens, to the point of eliminating the infected cells, adds Iannacone: “At the doses used, and in this modality, interleukin-2 acts only on the lymphocytes T which recognize hepatitis B antigens and this helps to avoid the side effects of widespread and non-specific activation of the molecule”. The team of scientists also tested the construct on human cells in vitro and on healthy macaques – with humanized molecules – demonstrating that it actually manages to expand, awaken, the population of immune cells of interest.

A possible “one-shot” therapy to eradicate the virus

The encouraging data for now stop at preclinical tests but the hope is that we can get to human trials. “We are awaiting the results of a phase I trial where the same molecule is tested against tumors – concludes the researcher – if positive they could also encourage trials against hepatitis B”. Opening the doors to immunotherapy against the virus: “Even a single administration could be enough to eradicate the virus if we were really able to mimic, thanks to immunotherapy, what happens in the acute form of the disease. And at that point – concludes the doctor – the treatment could also become attractive for healthcare systems”.

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