CAR-iNKT Immunotherapy cells as a HIV cure Intervention
The key barrier to HIV eradication is the presence of latently infected T cells within blood and tissue sites which act as a source of viral rebound on cessation of antiretroviral therapy and as a sanctuary for ongoing viral replication on ART. Innovative approaches to deplete the HIV reservoir are needed in addition to ART to reach a state of viral control off ART; or viral remission.
Chimeric Antigen Receptor (CAR) engineered T cells have been used successfully to treat lymphoma. However these cells a complex bespoke process which requires an allogenic transplant and engineering of T cells to circumvent the possibility of graft versus host disease. CAR-based therapy that employs a different kind of T cell, namely an invariant natural killer T cell (iNKT) offer the advantage that they don’t need to be harvested from the same patients in which they’re going to be used (i.e. they can be produced off the shelf); they can be taken from any healthy individual. For this reason, therapies based on iNKT cells hold the potential for easy and cheap mass production. One potential novel approach in HIV cure is the use of highly sensitive, HIV-specific genetically manipulated CAR-iNKT-cells. Research developing chimeric antigen receptor invariant natural killer T cells (CAR-iNKT) to target HIV is currently underway at Imperial College is led by Prof Karadimitris’s group at the Hammersmith campus in collaboration with Dr John Thornhill and Professor Fidler. Dr Thornhill is leading work to investigate if this technology is feasible in people living with HIV by assessing if these novel CAR-iNKT cells can access anatomical HIV reservoirs such as the gut and if these engineered CAR-iNKT have the potential to target HIV proteins and eliminate HIV infected cells.
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