The Tumour Microenvironment of Oesophageal Cancer

  • Research type

    Research Study

  • Full title

    Upregulation of innate immunity in the tumour microenvironment of oesophageal cancer using oncolytic virus therapy in combination with immunotherapy

  • IRAS ID

    270878

  • Contact name

    Hardev Pandha

  • Contact email

    h.pandha@surrey.ac.uk

  • Sponsor organisation

    University of Surrey

  • Duration of Study in the UK

    4 years, 0 months, 3 days

  • Research summary

    Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has produced dramatic and lasting responses for some cancer patients: ICIs are drugs that prevent the cancer cells sending a 'stop' signal to the immune system and thus keep the immune system 'switched on' to continue attacking and destroying the cancer. ICIs have proved revolutionary in the treatment of tumours such as melanoma, however response rates in Oesophageal cancers have so far been disappointing. In order to make immunotherapy more effect in oesophageal cancer this study will enhance our knowledge of the immune cells present in oesophageal tumours and identify potential targets for future therapies.

    We will examine the immune microenvironment of oesophageal cancer to understand what and how many immune cells are present in the tumours and how they might respond to immunotherapy. We will do this using archived oesophageal cancer tissue from patients who have previously undergone surgery to remove the cancer.

    We will aim to attract in more immune cells into the tumour microenvironment using an oncolytic ('cancer killing') virus. To examine the potential of this, we will incubate oncolytic virus on human oesophageal tumour tissue slices (ex-vivo) to identify if they are able to selectively infect the tumour cells. We will get fresh biopsies of oesophageal tumours that are surplus to diagnostic requirement taken during the operation to remove a patient's tumour.

    Finally we will examine the effect on oesophageal tumours of combining an oncolytic virus with an immune stimulating agent and ICI using a validated mouse model. We expect the virus will convert tumours into immunologically inflamed tumours. We will analyse the ability of these treatments to attract immune cells into the tumour, and whether this results in shrinking the tumour. We hope that this will result in a strong and long term anti-tumour response that will translate in patients.

  • REC name

    North of Scotland Research Ethics Committee 2

  • REC reference

    19/NS/0196

  • Date of REC Opinion

    20 Dec 2019

  • REC opinion

    Favourable Opinion