Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System

Title:Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System

Volume: 18 Issue: 2

Author(s): Vincenzo Cerullo*, Cristian Capasso, Markus Vaha-Koskela, Otto Hemminki and Akseli Hemminki*

Affiliation:

• Laboratory of Immunovirotherapy, Center for Drug Research and Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki,Finland

• Cancer Gene Therapy Group, Transplantation Laboratory and Haartman Institute, University of Helsinki,Finland

Keywords: Oncolytic adenovirus, gene therapy, innate immune system, adaptive immune system, pattern recognition receptors, armed oncolytic adenovirus, toll-like receptors.

Abstract: Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen- presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a “personalized in situ vaccine” for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit. Tackling these questions will give us further insight in how to manipulate adenovirus-mediated immune responses for enhancement of anti-tumor efficacy.

In this review, we first highlight how oncolytic adenovirus interacts with the innate immune system and its receptors such as Toll-like receptors, nucleotide-binding and oligomerization domain (NOD)- like receptors and other immune sensors. Then we describe the effect of these interactions on the adaptive immune system and its cells, especially B and T lymphocytes. Finally, we summarize the most significant preclinical and clinical results in the field of gene therapy where researchers have engineered adenovirus to manipulate the host immune system by expressing cytokines and signalingmediators.

Cite this article as:

Cerullo Vincenzo *, Capasso Cristian , Vaha-Koskela Markus , Hemminki Otto and Hemminki Akseli *, Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System, Current Cancer Drug Targets 2018; 18 (2) . https://dx.doi.org/10.2174/1568009617666170502152352