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Enhancing Oncolytic Virus-induced Immunotherapy using Eicosapentaenoic Acid (EPA)


Project Description

Breast cancer is the most commonly diagnosed cancer in women with triple-negative breast cancer (TNBC) having the worst prognosis, highest death rate and lowest overall survival. Therefore, novel treatments with limited toxicity and increased effectiveness are urgently required. Oncolytic viruses (OVs), which replicate preferentially in cancer cells, causing cell death, and induce anti-tumour immunity (thereby acting as immunotherapeutic tools) (1) have been investigated as anti-cancer agents for many years and their safety and efficacy has been reported in numerous OV clinical trials. Over the last decade, cancer immunotherapy has revolutionised cancer treatment for a range of cancers, and OV-induce immunotherapy has the potential to do so for breast cancer patients in the future. However, it is clear that complementary combination therapies are required to harness their full potential.

TNBC cells utilise multiple mechanisms to evade immune-mediated killing, including cyclooxygenase (COX)-2 mediated production of prostaglandin E2 (PGE2) which promotes an immunosuppressive tumour microenvironment (2). Recent pre-clinical and clinical data has demonstrated that the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), can reduce PGE2 production by COX-2 and displays significant anti-inflammatory and anti-cancer activity (3). Therefore, we believe that co-administration of EPA with OV could increase their therapeutic efficacy through improvement of OV-induced anti-tumour immune responses. In support of this current hypothesis we have already confirmed that PGE2 inhibits OV-induced immune activation, and that EPA can decrease the production of PGE2 from TNBC cells. Therefore, the aim of this PhD project is to establish whether EPA-downregulation of PGE2 can restore immune cell function and promote OV-induced immunotherapy. Ultimately this work aims to support the development of novel clinical strategies which will use EPA to potentiate OV-induced immunotherapy. Successful applicants will learn sterile tissue culture techniques for cancers cell growth and maintenance of immune cells, flow cytometry for cell phenotyping, and immunoassays, including ELISA.

Eligibility
You should hold a strong first degree equivalent to at least a UK upper second class honours degree in a relevant subject area.

The Faculty minimum requirements for candidates whose first language is not English are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

How to Apply
To apply for this scholarship applicants should complete a Faculty Scholarship Application form using the link below https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form and send this alongside a full academic CV, degree certificates and transcripts (or marks so far if still studying) to the Faculty Graduate School

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to

If you have already applied for other scholarships using the Faculty Scholarship Application form this academic year you do not need to complete this form again. Instead you should email to inform us you would like to be considered for this scholarship project.

Any queries regarding the application process should be directed to

Funding Notes

This project is available for self funding applicants only

References

1. Parrish C, Scott GB, Migneco G, Scott KJ, Steele LP, Ilett E, et al. Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia. Leukemia 2015;29(9):1799-810.
2. Zelenay S, van der Veen AG, Bottcher JP, Snelgrove KJ, Rogers N, Acton SE, et al. Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity. Cell 2015;162(6):1257-70.
3. Cockbain AJ, Volpato M, Race AD, Munarini A, Fazio C, Belluzzi A, et al. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut 2014;63(11):1760-8.

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