DATE: January 25, 2018
TIME: 10:00am PST, 1:00pm EST, 6:00pm GMT

Oncolytic virotherapy, the use of viral vectors to treat cancer, holds huge promise. Viruses are natural DNA delivery vehicles evolved to target specific tissues and transform them. Oncolytic virotherapies harness these abilities for therapeutic rather than pathological results. By engineering the virus to target cancerous cells rather than healthy cells we can create virotherapies which self-amplify at the point of need. Whilst historically safety focused, the field has now pivoted to enhanced efficacy following the first approved oncolytic virotherapy, T-VEC, for melanoma.

Our laboratory develops Adenoviruses (Ads) as oncolytics. Ads are versatile platforms offering large transgene capacity, ease of manipulation, and lytic potential with an excellent safety profile. However, current Ad-based therapies are hampered by high levels of pre-existing immunity within the population and off-target effects caused by the promiscuity of Ads’ canonical receptor: CAR.

We address these issues by a “bottom up” engineering approach to enhance the well characterised Ad5 serotype combined with a “top down” investigation of understudied Adenoviruses with advantageous phenotypes. By engineering Ad5 we can ablate natural tropism and facilitate specific infection of cancer cells; demonstrated by both in vitro, and in vivo models of cancer. Concurrently, we can develop rare Adenovirus serotypes devoid of pre-existing immunity, namely neutralising antibody activity. Integrating proteins from these serotypes into therapeutic vectors enables us to radically improve cancer cell transduction.

Once targeted, the viruses must be capable of efficient cancer cell killing. We have developed Ad vectors with a variety of transgenes to manipulate signalling pathways for therapeutic benefit. Current research focuses on combining the above aptitudes into a single virus with a 3-pronged therapeutic action:

• Inherent viral immunogenicity

• Direct cancer cell lysis

• Stimulation of anti-tumour immunity

Key Learning Objectives:

• Understand how protein engineering can be used to generate tissue specific viruses.
• Learn how re-engineered viruses can be used as cancer therapies.