Title:Nucleic Acid Sensing Machinery: Targeting Innate Immune System for Cancer Therapy
Volume: 13
Issue: 1
Author(s): Sandra Iurescia*, Daniela Fioretti and Monica Rinaldi*
Affiliation:
- Institute of Translational Pharmacology (IFT), Department of Biomedical Sciences, National Research Council (CNR), via Fosso del Cavaliere 100 - 00133 Rome,Italy
- Institute of Translational Pharmacology (IFT), Department of Biomedical Sciences, National Research Council (CNR), via Fosso del Cavaliere 100 - 00133 Rome,Italy
Keywords:
cGAMP, cGAS, cyclic dinucleotides (CDNs)-based adjuvants; immuno-oncology agents, innate immunity, RIG-I,
STING.
Abstract: Background: Nucleic acid sensing is an essential strategy employed by the innate immune
system to detect both pathogen-derived nucleic acids and self-DNA released by host apoptotic or necrotic
cells. The presence of nucleic acids that gain access to the cytoplasm is perceived by mammalian
cells as “stranger” or “danger” signals that trigger a myriad of immunological responses.
Recent publications have highlighted the importance of nucleic acid sensing machinery as mediator of
innate and adaptive immunity, and cGAS, STING and RIG-I agonists have been validated as immunooncology
agents in cancer therapy.
Objective: The crucial role of cGAS and STING in eliciting innate and adaptive immune responses
provides a scientific rationale for using cGAMP and STING agonists both in human preventive vaccine
and immunotherapy settings.
Thus, search for natural and synthetic STING agonists and development of cyclic dinucleotides
(CDNs)-based adjuvants were strongly intensified. Furthermore, with their ability to induce tumour cell
death and lymphocyte cross priming, RIG-I ligands are among the most promising molecules for the
development of new immunostimulatory adjuvants in cancer vaccines.
Results: This work focuses on relevant recent patents (2010-2017) that entail the use of nucleic acid
sensing machinery to elicit innate and adaptive immune responses, highlighting a new approach in
immune-mediated cancer therapy. Several patents describe compositions and methods that may be used
as immuno-oncology agents for the treatment of cancer patients. cGAS and/or STING pathways modulating
compounds alone or in combination with pharmaceutical compositions are discussed. New approaches
to improve DNA-vaccine induced adaptive immunity for cancer therapy through increasing
the level of plasmid-mediated activation of innate immune signalling pathways are also discussed.
In addition, a targeted selection of very recent clinical studies describing the employment of innate
immunity targeting compounds is reported.
Conclusion: It is highly relevant to deepen the study of the nucleic acid-sensing mechanisms to develop
new pharmacological approaches to engage these pathways within the tumour microenvironment.
Indeed, further clarification will be functional to develop advanced anticancer strategies or to
design new vaccine formulations.
