Oncolytic virusesHi all, for those awaiting the forthcoming...

Oncolytic viruses

Hi all, for those awaiting the forthcoming Vaxinia Results it could be worth taking some time out again to explore oncolytic viruses (OV’s) and how they work. For those seeking to do so, this informative scientific article is brilliant.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847443/#:~:text=OVs%20have%20been%20explored%20as,tumor%20cell%20antigens%20%5B98%5D

Clearly the exciting thing about OV’s such as Vaxinia is that unlike many cancer vaccines, monoclonal antibodies, and other forms of treatment such as chemotherapy and radiotherapy. Whilst many immunotherapies including monoclonal antibodies such as Keytruda are designed to boostthe body’s immune system to protect itself from carcinogenesis and progression of cancer, they often impact the healthy cells in a cancer patients body, hence the unnecessary side effects prevalent as a consequence of treatment. Yet as the article notes OVs are tumor-selective, thus in situ cancer vaccines, providing higher cancer specificity and better safety margin. Second, immunogenic/inflammatory types of cell death, including recently characterized “immunogenic cell death” (ICD) of cancer and stromal cells induced by OVs provides a natural repertoire of tumor-associated antigens (TAAs) in conjunction with danger signals [damage-associated molecular pattern (DAMP) and OV-derived pathogen-associated molecular pattern (PAMP) molecules, and inflammatory cytokines], to elicit anti-tumor immunity.

I note here other pieces of useful information I found in this coverage of OV’s :

1. OVs possess the ability to selectively infect and replicate in cancer and associated endothelial cells and kill these cells in cancerous tissues while leaving normal tissues unharmed

2. Cancer cell death induced by OVs is mostly immunogenic. Interestingly, a significant portion of the in vivo tumor killing activity by OVs, e.g., vesicular stomatitis virus (VSV) and vaccinia virus (VV), is caused by indirect killing of uninfected tumor cells

3. An OV, delivered either intratumorally or systemically, reaches to tumor tissue and selectively replicates in tumor or/and stromal cells. This leads to induction of death of these cells, presenting “eat me” signals on the cell surface and later release of danger signals from necrotic cells

4. In summary, ICD and autophagy triggered by a number of OVs provide a highly favourable backdrop for the immune system to respond and generate a potent adaptive anti-tumor immunity

5. In the tumour micro environment (TME) and associated signalling pathways can be manipulated to activate anti-tumor immunity in a therapeutic regimen. Thus, a number of immunotherapeutic strategies are aimed to disrupt the immune-regulatory circuits that are critical for maintaining tumor tolerance, such as CTLA-4 and PD-1, and augment protective anti-tumor immunity

6. Viruses have evolved with genes to suppress the immune system in order to survive and gain maximum replication in the hosts. In the context of OVs, they may play yin-yang roles. On one hand, they may increase viral persistence in the tumor leading to better oncolysis; while on the other hand, they may inhibit the immune response to both the virus and cancer, and thus reduce the potency of anti-tumor immunity. The balancing act between the two is not only a science, but also an art

7. The genetically engineered vaccinia virus (VV) is another good example. The deletion of viral genes encoding thymidine kinase (tk) and vaccinia growth factor (vgf) makes it a highly tumor-selective one, called vvDD [114]. These mutations restrict virus replication to cells that overexpress E2F (positively regulate cellular TK expression) and have constitutively activated epithelial growth factor receptor pathway. When it is armed with GM-CSF gene, its antitumor immunity and cytotoxicity were further enhanced

The article continues on to discuss combinations which may enhance the effectiveness of OV’s, as YF is aiming to do with Vaxinia. But my major take away is that OV’s such as Vaxinia are essentially living organisms within our body that not only serve to stimulate the immune system as traditional immunotherapies aim to do, they have this innate ability to kill both infected and uninfected tumour cells, with the potential to continue replicating and replicating over time until every time a tumour rears its ugly head, the virus says, “Oh no you don’t”.

DYOR