Harnessing innate immunity: natural killer cells and innate immune responses in reservoir clearance

As the HIV pandemic persists in the absence of an effective vaccine, this review summarizes promising recent strategies harnessing natural killer cells as part of the innate immune system for HIV cure.

Current HIV cure approaches aim to enhance natural killer (NK) cell function by reversing inhibition, cytokine-mediated activation and targeting reservoir tissues. Additionally, HIV-specific NK cell therapies include broadly neutralizing antibody-mediated antibody-dependent cellular cytotoxicity, bispecific antibodies and adoptive NK cell transfers. To date, none of the strategies by themselves showed sufficient efficacy, highlighting the importance of integrated approaches combining multiple NK cell-based strategies as well as considering the interplay between the innate and adaptive immune response to HIV-1.

Encouraging findings from in vitro studies, animal models and clinical trials studying innovative NK cell-based therapies demonstrate their potential for cure strategies. Different strategies may need to be combined to create synergy to overcome the major challenge represented by the latent viral reservoir.