Beneficial Uses of Viruses Part 2: Cancer Prevention/Treatment

What are virus-based strategies to treat or prevent cancer? (3)

prophylactic vaccines

oncolytic viruses

viral vector for therapeutics

What can some viruses cause?

cancer

What type of cancer can HPV cause?

cervical cancer

How does viral carcinogenesis work?

normal cell - affected cell (viral integration) - chronic/transforming infection - pre-cancer - genomic instability - cancer

Hepatitis B can cause what type of cancer?

hepatocellular carcinoma

What type is the hepatitis B vaccine?

either inactivated with recombinant antigens or recombinant vaccine with antigens

Why can HPV cause cervical cancer?

it can integrate in multiple genome locations

Gardasil is an HPV vaccine that can protect against how many strains?

9

What type of vaccine is Gardasil 9?

subunit vaccine

What is an oncolytic virus?

a virus that can preferentially infect and kill cancer cells

What else is useful about oncolytic viruses other than killing cancer cells?

they are immunogenic and can recruit immune cells to the site of the tumor

How can oncolytic viruses be engineered to target tumours?

use recombinant DNA technology to engineer tumor selectivity

What was the first oncolytic virus approved by the FDA, and what cancer does it work against?

T-VEC or Imlgic - inoperable melanoma

What type of virus was engineered for T-VEC?

a herpes virus

What factors affect oncolytic therapies?

suscesptibility

resistance

physical barriers

How does susceptibility affect oncolytic therapies?

tumour cells may have:

defective antiviral response (decreased IFN)

enhanced expression of a surface protein that a virus uses for entry

How does resistance affect oncolytic therapies?

diversity of genetics and epigenetics in tumours

How do physical barriers affect oncolytic therapies?

interstitial fluid pressure

extracellular matrix

tight junctions

Why can T-VEC only replicate in cancer cells?

the gene that blocks the stress reponse and would allow it to replicate in healthy cells is removed

Why can T-VEC not infect healthy cells?

it is genetically engineered to lack the ICP34.5 gene, which is essential for overcoming the antiviral defenses of healthy cells

How can viral vectors be used to deliver anti-cancer therapies?

using the virus's natural ability to enter cells while removing its pathogenic genes - oncolytic viruses and gene therapy