Harnessing natural killer cells to eliminate HIV

A ‘sterilising’ cure for HIV requires the elimination of all cellular sources of HIV, including those which persist in long-lived cells. Achieving this will likely require dedicated strategies to enhance the ability of the body’s immune system to recognise and kill HIV-infected cells.

Natural killer (NK) cells are innate immune cells which can kill virally-infected cells by antibody-dependent cellular cytotoxicity (ADCC), where they recognise target cells coated with antibodies. ADCC is associated with both HIV control and protection and is a promising strategy for targeting HIV-infected cells, particularly macrophages which are a type of immune cell infected by HIV that shows resistance to cell death.

We are investigating antibodies which bind to the HIV envelope (Env) protein expressed on HIV-infected cells and facilitate NK cell-mediated elimination by ADCC. We are working to enhance the function of both these antibodies and NK cells themselves to develop a potent immunotherapy-based approach to eliminate challenging and persistent sources of HIV, such as found in macrophages.

Objective

This project aims to develop ‘weaponised’ anti-Env antibodies and identify NK cell subpopulations which can effectively target and eliminate HIV-infected cells, including macrophages.

Timeline

2022–ongoing.

Approach

We aim to: