Killing of HIV-infected cells for HIV cure

Using bi-specific reagents, this project will enable immune cells to kill HIV-1-infected cells. These new reagents are developed together with the collaborator Harbour BioMed Netherlands BV, a global, clinical stage biopharmaceutical company, which is committed to development and commercialisation of new therapeutic antibody therapies.

Human immunodeficiency virus (HIV-1) infections have significant health and economic implications worldwide. HIV-1 infected individuals are treated with combined antiretroviral therapy. These medicines stop the spread of the virus, but are not enough to cure the HIV-1 infection. This is because HIV-1 can reside in immune cells of an infected person for years, called the dormant HIV reservoir. In order to cure HIV, these cells harboring the “sleeping virus” must be destroyed. This can be done by awaking first the HIV virus with drugs and then killing them by the immune system.

Eliminating these re-activated cells still proves to be very difficult. In this research project, they will develop reagents that can facilitate this elimination step. They do this by binding with one arm to virus on infected cells and by binding to the body's own killer cells with the other arm. This brings the two cells close together which allows the killer cells to destroy the infected cells. Eradicating the dormant HIV reservoir will have major consequences for HIV-1 infected individuals. HIV infection carries a stigma and this can have a negative impact on the lives of HIV-infected people. HIV cure also gives a better clinical outcome compared to treatment of chronic HIV infection. In addition, HIV cure would reduce health care costs, as lifelong cART treatment is no longer necessary.

At the end of the project, they envision to have tested several different bi-specific reagents, targeting different immune cells and have validated which one is best in killing HIV-infected cells.