An old enzyme for current needs: adenosine deaminase and a dendritic cell vaccine for HIV

Abstract

After nearly three decades of searching for a vaccine against HIV, a cure for this pandemic disease still remains elusive. The low immunogenicity of the surface proteins and the huge variability of the virus, together with the immunocompromised status of the host, have made developing an HIV vaccine an uphill battle. Over the past few years, both immunogen design and immunization strategies have improved, providing hope for future, although the anti‐HIV responses achieved still remain modest. As developing a prophylactic vaccine seems unlikely nowadays, efforts have focused on alternative therapeutic immunization approaches, although these still need to be further optimized. Using an immunomodulator capable of restoring immune function in the context of infection, thereby boosting cell‐mediated and humoral responses, could be critical in effectively improving current therapeutic approaches. Adenosine deaminase, a protein with a pivotal role in T‐cell co‐stimulation, has been shown to robustly enhance specific T‐cell responses against HIV in vitro. Although its role in humoral responses has not yet been assessed, genetic defects in this enzyme are associated with impaired cellular and humoral responses. Importantly, this molecule is already commercially available pharmaceutically and, therefore, it fulfils all the requirements to be assayed as an anti‐HIV vaccine adjuvant.

Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass

“…In our current study we demonstrate an elevation in several genes associated with T-cell activation and signaling preoperatively in patients that would later develop NCD. For instance, patients who developed NCD postoperatively had significantly elevated regulation in genes implicated in T-cell activation, maturation, and cytokine signaling including ADA, CD3E, CD3G, IL2RG, IL32, NFATC2, and STAT4 18–20 . Perhaps these inherent elevations result in accentuated inflammatory response and resultant increase in chemokine production.…”

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

“…As a whole, these effects suggest that ADA, as a costimulator, might promote enhanced and correctly polarized HIV‐specific T‐cell responses, targeting asymptomatic HIV‐infected individuals. Since ADA robustly enhanced specific T‐cell responses against HIV in vitro and is already commercially available pharmaceutically, it has been suggested that this enzyme fulfills all the requirements to be assayed as an anti‐HIV vaccine adjuvant . CD26 also plays an important role in tumor biology, and the CD26–ADA complex is selectively expressed on anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma and Hodgkin's lymphoma .…”

Adenosine Receptor Antagonists to Combat Cancer and to Boost Anti-Cancer Chemotherapy and Immunotherapy

“…At first, it was noticeable the identification of interaction of ADA1 with an AR, but indeed the enzyme may interact with more than one AR type. It is now known that the functionality of ARs is regulated by the enzymatic and extra-enzymatic action of ADA1, and that this is of special relevance in the immune system [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]. May inhibition of ADA1 be useful to combat cancer when Ado is friend?…”