JAN 25, 2018 10:00 AM PST

WEBINAR: Engineered Viruses as Precision Cancer Therapeutics

Speaker
  • PhD Researcher
    Biography
      Alex's research is in the nascent field of oncolytic virotherapy, utilizing re-engineered adenoviruses to specifically target and destroy cancer cells. He gained his first degree at the University of Aberdeen in Scotland. Having published research on novel mechanisms of bacterial antibiotic resistance, he joined Absolute Antibody where he developed sophisticated antibody engineering techniques which continue to address a variety of industrial needs. He then returned to Aberdeen to work with Dr Frank Ward on the immune co-checkpoint inhibitor sCTLA-4.
      In 2015, Alex moved to lab of Dr Alan Parker at Cardiff University where he combined his experience of protein engineering and cancer immunology in the development of new virotherapies. He believes that the interdisciplinary approach available in the lab will accelerate the innovative treatments under development there to a translational benefit. As well as his Cardiff based research, Alex maintains an active collaboration with Dr Mitesh Borad at the Mayo Clinic developing next generation antibody therapies for genetically defined cancers.
      Aside from his research responsibilities Alex is passionate about science communication and public engagement. He has run patient engagement days for those with the diseases he works on and organized the first ever Welsh Pint of Science festival to a sold-out audience. Most recently, Alex has been appointed to the board of the British Society of Gene and Cell Therapy (BSGCT) as Early Career Representative where he is responsible for engagement with scientists starting out in the field.

    Abstract

    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.

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