Development of therapeutic vaccines for MAGE-expressing tumours

Project Overview

The clinical success of immune checkpoint inhibitors (CPIs) in treating advanced cancer patients marks a major breakthrough in cancer immunotherapy. However, only a subset of patients respond to the treatment and the efficacy of CPIs depends on pre-existing anti-tumour T cell responses. Cancer vaccines have the potential to induce tumour-specific immune responses to reject tumours. The MAGE-type antigens including MAGE-A3 and NY-ESO are aberrantly expressed in a wide variety of human malignancies, but not in normal

tissues with the exception of male germline cells and trophoblastic tissues. These two cell types do not express MHC molecules and thus cannot present these antigens to T cells. MAGE-A3 and NY-ESO share strong similarity with the mouse P1A antigen, including the pattern of expression. The P1A antigen has been widely used in experimental mouse tumour models. Our lab has generated new MAGE-targeting cancer vaccines optimized to induce strong cytotoxic T lymphocyte (CTL) responses. We are using an effective viral vector platform and different immunogen design to induce potent CTL responses against tumours. This project aims at testing the combination of MAGE-targeting cancer vaccines with other therapies (e.g. CPIs) to boost anti-tumour immunity and improve efficacy. Different mouse tumour models will be employed to assess the vaccine efficacy and to decipher the mechanisms. This study will lay the foundation for clinical testing of therapies in cancer patients.

References

Cappuccini F, Pollock E, Stribbling S, Hill AV, Redchenko I. 2017. 5T4 oncofoetal glycoprotein: an old target for a novel prostate cancer immunotherapy. Oncotarget8(29), pp. 47474-47489.

Cappuccini F, Pollock E, Stribbling S, Hill AV, Redchenko I. 2016. Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer. Cancer Immunol Immunother., 65(6), pp. 701-713.

Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T. 2014. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer14(2), pp.135-46.

Zhu J, Powis de Tenbossche CG, Cané S, Colau D, van Baren N, Lurquin C, Schmitt-Verhulst AM, Liljeström P, Uyttenhove C, Van den Eynde BJ. 2017. Resistance to cancer immunotherapy mediated by apoptosis of tumor-infiltrating lymphocytes. Nat Commun., 8(1), pp. 1404.

Training Opportunities

The student will work within a small team and will receive training in a wide variety of techniques involved in the project, including cell culture, molecular biology, multiparameter flow cytometry, cellular immunology. Also, the student will get Home Office Modular training to gain a Procedure Individual Licence for conducting animal research. In addition, our group will provide training on experimental design, data and statistical analysis, presentation and writing skills. 

Theme

Immunology & Infectious Disease and Cancer Biology

Admissions

Project reference number: 1019

Funding and admissions information

Supervisors

Name Department Institution Country Email
Professor Benoit Van Den Eynde Oxford Ludwig Institute Oxford University, Old Road Campus Research Building GBR benoit.vandeneynde@ludwig.ox.ac.uk
Dr Carol Leung Nuffield Department of Medicine Oxford University GBR carol.leung@ludwig.ox.ac.uk

There are no publications listed for this DPhil project.