Exploring combinations of cancer vaccines with chemotherapy and checkpoint inhibitors

Cancer vaccines have the potential to increase the clinical efficacy of cancer immunotherapy based on checkpoint inhibitors, because they can turn cold tumors into hot tumors that are more responsive to checkpoint inhibitors. Our lab has been developing cancer vaccines based on viral vectors (ChAdoX1 and MVA) targeting MAGE-type antigens, some of which are in clinical development. The deployment of cancer vaccines in the clinic needs to consider the standard of care of cancer patients, which usually comprises chemotherapy. Whether concurrent chemotherapy impacts on the efficacy of vaccination is not known. Common sense suggests that anti-proliferative drugs should negatively affect lymphocyte proliferation, and thereby impair vaccine immunogenicity. In contrast, our current results indicate that, when given together with the vaccine, chemotherapy based on carboplatin and paclitaxel increases vaccine immunogenicity by favoring the induction of stem-like T cells expressing TCF1.

This project will systematically explore the effect of other types of chemotherapy on vaccine immunogenicity and anti-tumor efficacy in preclinical mouse tumor models. The project will focus on chemotherapy regimens commonly used in the clinic and compare different schedules in which chemotherapy is given before, together or after vaccination. We will also model the effects of corticosteroids, which are often given together with chemotherapy to minimize toxicity. An analytic approach will be followed to understand the mechanistic aspects of the effects observed.

This work will inform the clinical development of cancer vaccines in combination with chemotherapy and checkpoint inhibitors. 

Funding Notes

Ludwig studentships provide 4 years funding for a tax-free stipend, currently £21,000 pa and university fees at home and international rates.

Only applications made by the University of Oxford application system for a DPhil in Clinical Medicine will be considered. You may apply for a maximum of two Ludwig projects. Under proposed field and title of research project please enter the project titles in the order of preference. You do not need to provide a research proposal but must include a personal statement.

Please ensure referees are willing to write and submit your reference by the deadline.

Enquiries

Alexandra Royer – alexandra.ward@ludwig.ox.ac.uk – application related enquiries

Applications

https://www.ox.ac.uk/admissions/graduate/courses/dphil-clinical-medicine