Using Dendritic Cell-Based Immunotherapy to Treat HIV: How Can This Strategy be Improved?

Abstract

Harnessing dendritic cells (DC) to treat HIV infection is considered a key strategy to improve anti-HIV treatment and promote the discovery of functional or sterilizing cures. Although this strategy represents a promising approach, the results of currently published trials suggest that opportunities to optimize its performance still exist. In addition to the genetic and clinical characteristics of patients, the efficacy of DC-based immunotherapy depends on the quality of the vaccine product, which is composed of precursor-derived DC and an antigen for pulsing. Here, we focus on some factors that can interfere with vaccine production and should thus be considered to improve DC-based immunotherapy for HIV infection.

Keywords: HIV; clinical trial; dendritic cells; immunotherapy; therapeutic vaccine.

Figure 1

Challenges in dendritic cell immunotherapy for HIV infection. There are many factors that should be considered in the production of DC-based vaccines to achieve a sufficient immune response against HIV combined with viral load control. In general, these can include elements related to the individual patient (A), such as genetic factors, clinical status, and drug treatment (cART interruption or not after receiving the immunization). In addition, the range of antigens available to pulse DC is extensive, making it a challenge to choose the best one (B). The factors related to the vaccine product (B,C) are just as important, including the choice of appropriate DC precursors (CD34+ cells or monocytes) and their differentiation/activation protocols (e.g., standard DC, α-DC1, IFN-DC), while also taking into account the potential of DC to produce exosomes (considering their role in regulation of the immune response) (C). In this context, proper assembly of each individual gear could achieve viral infection control and make possible the “functional cure” (D).