Dr Gunnel Halldén

PhD
Reader in Cancer Gene Therapy
Group Leader
Twitter
Research Focus

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.

Key Publications

The novel oncolytic adenoviral mutant Ad5-3Δ-A20T retargeted to αvβ6-integrins efficiently eliminates pancreatic cancer cells. 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. 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. 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. Clin Cancer Res (2010) 16(2):541-53. PMID: 20068104

Major Funding
  • 2019-2022- 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
Other 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.
Research

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.

Other 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).

Teaching activities

  • Postgraduate tutor for the Centre of Molecular Oncology
  • Mentor for 1st and 2nd year Medical students at QMUL
  • Module 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.
Major Funding
  • 2019-2022- 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
Recent Publications

Advances in oncolytic adenovirus therapy for pancreatic cancer. Nattress CB, Halldén G Cancer Lett (2018) 434(2) 56-69
https://www.ncbi.nlm.nih.gov/pubmed/29981812

Designer Oncolytic Adenovirus: Coming of Age. Baker AT, Aguirre-Hernández C, Halldén G et al. Cancers (Basel) (2018) 10(2)
https://www.ncbi.nlm.nih.gov/pubmed/29904022

The Novel Oncolytic Adenoviral Mutant Ad5-3Δ-A20T Retargeted to αvβ6 Integrins Efficiently Eliminates Pancreatic Cancer Cells. Man YKS, Davies JA, Coughlan L et al. Mol Cancer Ther (2018) 17(2) 575-587
https://www.ncbi.nlm.nih.gov/pubmed/29367266

Sensitisation to mitoxantrone-induced apoptosis by the oncolytic adenovirus Ad∆∆ through Bcl-2-dependent attenuation of autophagy. Aguirre-Hernández C, Maya-Pineda H, Millán JS et al. Oncogenesis (2018) 7(2) 6
https://www.ncbi.nlm.nih.gov/pubmed/29362360

Targeting pancreatic and prostate cancer with E1B19K-deleted oncolytic adenoviruses Hallden G HUMAN GENE THERAPY (2017) 28(1) A6-A6

The adenoviral Ad Delta Delta mutant enhances mitoxantrone-induced apoptosis and attenuates drug-induced autophagy in prostate cancer cells. Aguirre-Hernandez C, Millan JS, Hallden G (2016) (11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000388119200298&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

The adenoviral AdDD mutant enhances mitoxantrone-induced cell death by promoting apoptosis and attenuating autophagy in prostate cancer cells. Hernandez CA, Hallden G HUMAN GENE THERAPY (2016) 27(11) A5-A6
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000380615900013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

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 et al. Oncotarget (2016) 7(2) 15703-15724
https://www.ncbi.nlm.nih.gov/pubmed/26872382

Oncolytic adenoviral mutants deleted in the anti-apoptotic E1B19K gene sensitize pancreatic cancer cells to drug-induced DNA damage Pantelidou C, Man YKS, Coughlan L et al. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE (2016) 38(11) S58-S58
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000383733000215&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Oncolytic adenovirus-mediated therapy for prostate cancer. Sweeney K, Halldén G Oncolytic Virother (2016) 5(2) 45-57
https://www.ncbi.nlm.nih.gov/pubmed/27579296

For additional publications, please click here
Team

Postdoctoral Researchers
Dr Lauren Maskell

Medical BSc student
Mr Callum B. Nattress

Visiting postgraduate MSc student
Ms Ines Garcia Rodriguez

Biography

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.