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Cancer: Enhancing reovirus immunotherapy with eicosapentaenoic acid (EPA)

PGR-P-58

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Funding
Non-funded
Supervisors
Dr Fiona Errington-Mais and Dr Milene Volpato
Additional supervisors
Dr Fiona Errington-Mais, Dr Milene Volpato
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Medical Research at St James's
<h2 class="heading hide-accessible">Summary</h2>

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. <br /> <br />

<h2 class="heading hide-accessible">Full description</h2>

<p>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). &nbsp; 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. &nbsp;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. &nbsp;Ultimately this work aims to support the development of novel clinical strategies which will use EPA to potentiate OV-induced immunotherapy. &nbsp;Successful PhD students will learn sterile tissue culture techniques for cancers cell growth and maintenance of immune cells, flow cytometry for cell phenotyping, and immunoassays, including ELISA. &nbsp;</p> <p><strong>In line with the bespoke nature of our International PhD Academy a modified PhD project can be proposed dependent on students interests and background.</strong></p> <h3>References</h3> <ol> <li>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.</li> <li>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.</li> <li>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.</li> </ol>

<h2 class="heading">How to apply</h2>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. To apply for this project applicants should complete an <a href="http://www.leeds.ac.uk/info/130206/applying/91/applying_for_research_degrees">online application form</a> and submit this&nbsp;alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates. Please make it clear in the research information section that you are applying for the International PhD Academy: Medical Research, as well as the title of the project you wish to be considered for.</p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &acirc;&euro;&cent; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &acirc;&euro;&cent; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

<h2 class="heading">Contact details</h2>

<p>Informal enquires about regarding the bespoke taught first year of the PhD programme and research projects can be made by contacting <a>LIMRPhD@leeds.ac.uk</a></p> <p>Enquiries regarding the application process should be directed to the Faculty of Medicine and Health Graduate School&nbsp;Office&nbsp;e: <a href="tel:0113 343 8221">fmhpgradmissions@leeds.ac.uk</a> t: +44 (0)113 343 8221.</p>


<h3 class="heading heading--sm">Linked research areas</h3>