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Monoclonal antibodies: short-term therapy for the long-term treatment of chronic viral infections?

11 June 2010 CNRS (Délégation Paris Michel-Ange)

Monoclonal antibodies are the largest class of biotherapeutic drugs. When administered to infected organisms to blunt the propagation of pathogenic viruses, they may also induce a long-lasting and protective antiviral immune response similar to that achieved by vaccination. These results obtained in mice by the "Oncogenèse et Immunothérapie" group at the Institut de Génétique Moléculaire de Montpellier (CNRS/Universités Montpellier 1 and 2), have been published on 10 June in PLoS Pathogens. They raise hopes for the treatment of certain severe and chronic viral infections.

Antibodies (AB) are molecules that are produced by the immune system to defend itself against cancer cells and infective agents. Of these, monoclonal antibodies1 can be developed and produced at a large scale to treat a variety of diseases: cancer, inflammatory or infectious diseases, etc. They thus constitute the largest class of biotherapeutic drugs to date and are being considered with increasing interest for the treatment of severe and chronic viral infections such as HIV (Human Immunodeficiency Virus) or HCV (Hepatitis C Virus), against which current therapies are still insufficient.

Until now, the only mechanism of action of antiviral monoclonal antibodies that was really considered by the medical and scientific communities was the neutralization and direct elimination of viruses in infected organisms.

Using a model of viral leukemia in mice, the "Oncogenèse et Immunothérapie" group at the Institut de Génétique Moléculaire in Montpellier (CNRS/Universités Montpellier 1 and 2), headed by Marc Piechaczyk, has recently shown that under certain conditions, a very short course of treatment (a few days) with antiviral monoclonal antibodies can have an additional effect similar to that of a vaccine. After three weeks, and even though the injected monoclonal antibodies had disappeared, the researchers indeed detected a potent and long-lasting (more than a year) antiviral immune response that was sufficient for the mice to avoid death from leukemia.

The team identified an unexpected mechanism enabling the monoclonal antibodies to induce protective antiviral immunity. This mechanism is based on their ability to recognize not only circulating viral particles but also certain viral proteins expressed at the surface of infected cells. These new findings may help to trigger protective immunity. They should be borne in mind by the biologists who design and develop therapeutic antiviral monoclonal antibodies.

In mice, a short and early course of therapeutic monoclonal antibodies targeting both the viruses and the cells infected by these viruses thus enables permanent recovery from a fatal chronic infection. If this observation can be extrapolated to humans, it will result in a therapeutic benefit not only for patients but also for society, in that it will help to significantly reduce the cost of monoclonal antibody therapies, which remains prohibitive in most cases.

1 Monoclonal antibodies are entirely pure antibodies that only recognize one type of antigen. Because of their specificity, which can easily be established, they are increasingly being used for therapeutic purposes for the selective destruction of tumor or viral cells and to combat certain inflammatory disease such as rheumatoid arthritis.

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