June 2021| Adenovirus Production - Research, Preclinical, Clinical

The induction of local and systemic anti-tumour immunity by oncolytic viruses.
The induction of local and systemic anti-tumour immunity by oncolytic viruses. The therapeutic efficacy of oncolytic viruses is determined by a combination of direct cancer cell lysis and indirect activation of anti-tumour immune responses. Upon  infection with an oncolytic virus, cancer cells initiate an antiviral response that consists of endoplasmic reticulum (ER) and genotoxic stress. This response leads to the upregulation of reactive oxygen species (ROS) and the initiation of antiviral cytokine production. ROS and cytokines, specifically type I interferons (IFNs), are released from the infected cancer cell and stimulate immune cells (antigen presenting cells, CD8+ T cells, and natural killer (NK) cells). Subsequently, the oncolytic virus causes oncolysis, which releases viral progeny, pathogen-associated molecular patterns (PAMPs), danger-associated molecular pattern signals (DAMPs), and tumour associated antigens (TAAs) including neo-antigens. The release of viral progeny propagates the infection with the oncolytic virus. The PAMPs (consisting of viral particles) and DAMPs (comprising host cell proteins) stimulate the immune system by triggering activating receptors such as Toll-like receptors (TLRs). In the context of the resulting immune-stimulatory environment, TAAs and neo-antigens are released and taken up by antigen presenting cells. Collectively, these events result in the generation of immune responses against virally infected cancer cells, as well as de novo immune responses against TAAs/neo-antigens displayed on un-infected cancer cells. CD40L, CD40 ligand; dsRNA, double-stranded RNA; HMGB1, high mobility group box 1; HSP, heat shock protein; IL-2, interleukin-2; IL-2R, IL-2 receptor; MHC, major histocompatibility complex; ssRNA, single-stranded RNA; TCR, T cell receptor; TNFα, tumour necrosis factor-α. (Figure 2, Nature Reviews Drug Discovery 14, 642–662 (2015))

 

 

Figure reprinted with permission from Springer Nature

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