Dr Gunnel Halldén

Dr Gunnel Halldén

PhD
Centre: Molecular Oncology
Reader in Cancer Gene Therapy
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QMUL Directory


The research in our team is focused on the development of novel treatment strategies to target prostate cancers and pancreatic cancers using genetically modified viruses that target, replicate and kill cancer cells (replication-selective oncolytic viruses) but leave normal cells unharmed.

Research Details

The recent market approval of the first oncolytic immunotherapy, the herpes virus (T-Vec), has demonstrated the feasibility and effectiveness of these biotherapeutics. The focus in our team is on developing potent oncolytic, anti-cancer immune boosting adenoviral mutants that act in synergy with current clinical therapeutics. The specific aims of the research are:

  • To construct highly tumour-specific and potent oncolytic viruses containing a combination of genetic changes - deletions, mutations, heterologous promoters and transgenes - for optimal efficacy in cancer tissue and for systemic delivery in patients with metastatic disease.
  • To determine cellular mechanisms for synergistic interactions of viral mutants with current therapeutics such as cytotoxic drugs, small molecule inhibitors and immune factors.
  • To dissect the molecular signalling pathways that cause enhanced cell killing including apoptosis and autophagy pathways with the aim of identifying novel targets for development of improved therapeutics.
  • To develop model systems for pancreatic and prostate cancer that enable testing of oncolytic viruses ex vivo in cancer cell lines and primary tumour cells.

The overall goal of the team is to develop improved therapies for late stage, currently treatment-resistant cancers, by constructing potent tumour specific oncolytic viruses to be investigated and evaluated in combination with therapeutics acting through different mechanisms.

Team members

Postdoctoral Researcher: Dr Lauren Maskell
Medical BSc student: Mr Callum B. Nattress
Visiting postgraduate MSc student: Ms Ines Garcia Rodriguez

Profile

I joined the Barts Cancer Institute, in November 2004, as a Lecturer starting a Cancer Gene Therapy team, funded by the Flavell Bequest Programme in Prostate Cancer Gene Therapy. I completed my BSc at the University of Stockholm and Karolinska Institute, and my PhD at UC Berkeley in the USA. My postdoctoral training was in endocrinology, and cell and molecular biology at UC Berkeley, in oncolytic viruses at Onyx Pharmaceuticals (Richmond, CA, USA) and the Molecular Oncology Unit at Hammersmith Hospital in London.

In 2008 I was awarded my PGCAP (Postgraduate Certificate in Academic Practice) in teaching and learning from QMUL. In 2014 I was promoted to Reader in Cancer Gene Therapy and have focused my work on developing improved treatments for currently incurable prostate and pancreatic cancers.

Funding

2019-2023 Pancreatic Cancer Research Fund (PCRF) "Identification of drugs that promote activation of the host anticancer immune-responses through enhancement of virus-mediated lysis"
£200,000
2019-2023 Prostate Cancer UK (PCUK) Innovation Award "Coating and modification of a prostate-selective oncolytic adenovirus to enable systemic delivery, eliminate metastases and induce tumour immunity"
£245,000
2016-2018 Barts Charity "Identifying new therapeutic strategies for late-stage prostate cancer patients using a unique ex vivo culture model that mimics the tumour environment in situ"
£142,000
2015-2016 Pancreatic Cancer UK "Targeting αvβ6-integrin expressing pancreatic cancers with a mutant adenovirus for imaging and therapy."
£75,000

2013-2016

The Prostate Cancer Charity PhD project: "Develop novel therapies for advanced prostate cancers by dissecting deregulated cell survival"
£99,996
2013-2014 Pancreatic Cancer Research Fund Extended PhD project 
£28,000
2012-2014 Pancreatic Cancer Research Fund Postdoctoral project: "Improved virotherapy for intefrin-expressing pancreatic cancers"
£149,687
2010-2013 Pancreatic Cancer Research Fund PhD project: "Targeting pancreatic cancer with oncolytic virotherapy and cytotoxic drugs identification of cellular mechanism and biomarkers for treatment responses"
£116,940

Key Publications

The novel oncolytic adenoviral mutant Ad5-3Δ-A20T retargeted to αvβ6-integrins efficiently eliminates pancreatic cancer cells. Man YKS, Davies JA, Coughlan L, Pantelidou C, Blázquez-Moreno A, Marshall JF, Parker A, Halldén G. Molecular Cancer Therapeutics (2018) 17 575-587. PMID: 29367266

Sensitisation to mitoxantrone-induced apoptosis by the oncolytic adenovirus Ad∆∆ through Bcl-2-dependent attenuation of autophagy. Aguirre-Hernández C, Maya-Pineda H, San Millán J, Man YSK, Lu YL, Halldén G. Oncogenesis (2018) 7(1):6. PMID: 29362360

The E1B19K-deleted oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11. Pantelidou C, Cherubini G, Lemoine NR, Halldén G. Oncotarget (2016) 7(13):15703-24. PMID: 26872382

Improved potency and selectivity of an oncolytic E1ACR2 and E1B19K deleted adenoviral mutant (AdΔΔ) in prostate and pancreatic cancers. Öberg D, Yanover E, Adam V, Sweeney K, Costas C, Lemoine NR, Halldén G. Clin Cancer Res (2010) 16(2):541-53. PMID: 20068104


Further Publications

For additional publications, please click here.


The research in our team is focused on the development of novel treatment strategies to target prostate cancers and pancreatic cancers using genetically modified viruses that target, replicate and kill cancer cells (replication-selective oncolytic viruses) but leave normal cells unharmed.

External Activities

Teaching activities

  • Postgraduate tutor for the Centre of Molecular Oncology
  • Mentor for 1st and 2nd year Medical students at QMUL
  • Co-lead on ‘Introduction to Cancer Biology’ for first year Medical students
  • Lead on MSc module ‘Drug Development’
  • Lecturing on Gene therapy, oncolytic viruses and cancer biology for MSc and BSc students at QMUL, Imperial College and the Royal Veterinary College
  • Supervising several BSc students (from European and Chinese Universities, the Royal Veterinary College and QMUL) in their last year research projects.

External Activities

  • Editorial Board Member: Molecular Therapy and Molecular Therapy – Oncolytics
  • Research Grant Reviewer for funding bodies including, the European Commission, the British Medical research Council (MRC), the INSERM (France), the World wide Cancer Research Organisation, the Skolkovo Organisation (Russia), and the British Society for Gene and Cell Therapy (BSGCT) research bursary.
  • Referee of scientific journals including Molecular Therapy, Nature Review Urology, Molecular Oncology, Oncotarget, Cancer Research, Gene Therapy, Human Gene Therapy, EMBO, Advances in Virology, Journal of Virology.
  • Active member of professional organisations including the American Society for Cell and Gene Therapy (ASGCT), the European and British Societies for Cell and Gene Therapy (ESGCT and BSGCT), the American Association for Microbiology (ASM).

News

  • 2019: Interview in the Evening Standard (22/01/19) regarding the new Prostate Cancer UK Innovation Award 
  • 2018: BBC radio interview and online in the ‘Naked Scientist’ (broadcast internationally) and publicity in several newspapers and online sites including the Independent, the Scotsman, ALN
  • 2018: Invited speaker to 13th International Adenovirus Meeting (IAM), Mexico City, Mexico: Enhanced replication of oncolytic AdΔΔ and Ad-3Δ-A20T promotes spread in 3D models of the tumour microenvironment.
  • 2017: Radio interview for Swedish Radio, broadcast March 28-April 4, discussing Pancreatic Cancer.
  • 2017: British Society for Gene and Cell Therapy (BSGCT), Cardiff, UK: Targeting prostate and pancreatic cancer with oncolytic adenoviral mutants deleted in the anti-apoptotic E1B19K gene.
  • 2017: Oncolytic Virotherapy Europe Congress 2017, London, UK: Targeting cancer with oncolytic adenoviral mutants deleted in the anti-apoptotic E1B19K gene.
  • 2016: The 7th Piraeus Seminar on Oncology, Athens, Greece: Oncolytic adenoviruses for pancreatic cancer.
  • 2016: The 22nd World congress on Advances in Oncology and International Symposium on Molecular Medicine, Athens, Greece: Cancer gene therapy: Targeting prostate and pancreatic cancer with oncolytic viruses.
  • 2016: News article by PCRF journalist regarding our publication in Oncotarget Feb 10 (2016), PMID:26872382. Published in Science Daily and PCRF website
  • 2016: Invited Guest Lecturer on The Advanced Course in Clinical and Molecular Virology in Porto, Portugal to lecture on ‘Oncolytic viruses targeting prostate and pancreatic cancer.’
  • 2016: Oral presentation at the BSGCT in London of recent research ‘The AdΔΔ mutant enhances mitoxantrone-induced apoptosis and attenuates autophagy in prostate cancer.’
  • 2015: Invited speaker at the ESGCT conference in Helsinki, Finland ‘The oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11.
  • 2014: Presented two posters at the 8th International Meeting on Replicating Oncolytic Virus Therapeutics (April, 2014), Oxford UK.  'Oncolysis is greatly enhanced by retargeting of replication-selective adenoviral mutants to avß6-integrin expressing cancers and 'Adenoviruses deleted in the anti-apoptotic E1B19K-gene synergise with DNA-damaging drugs through attenuation of DNA-damage repair responses and checkpoint activation'
  • 2013: Invited speaker at the 7th International Meeting on Replicating Oncolytic Virus Therapeutics (June 15-18, 2013), Québec City, Canada. Seminar on ‘The oncolytic mutant Ad∆∆ synergises with cytotoxic drugs through induction of apoptosis, attenuation of autophagy and aberrant mitosis in prostate and pancreatic cancer models’.
  • My work funded by Prostate Cancer UK
  • A video of my work funded by the Pancreatic Cancer Research Fund can be found here.

See other researchers working on:

Gene Therapy Genitourinary Cancer Pancreas Prostate Viruses
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