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Cancer Gene Therapy

Why we focus Cancer Gene Therapy

Despite advances in our understanding of the processes involved in the development and progression of cancer, treatment options for many patients are limited and prognosis still remains poor. Surgery followed by chemotherapy or radiation therapy have been the main treatment options available for cancer patients, however many cancers are resistant to these standard therapies. At the BCI, we are developing experimental treatments that can target these resistant cancers.  We are particularly focusing on development of gene therapy strategies to target pancreatic, prostate and ovarian cancers, which have mortality rates that have not significantly improved in the past two decades.

What we do

  • The gene therapy program focuses on the development of engineered viruses that selectively replicate in and kill cancer cells (oncolysis).
  • We use Adenovirus and Vaccinia virus, which we are modifying to enhance oncolytic efficacy against tumour cells, while maintaining safety. These viruses are used to deliver genes designed to influence the tumour environment and improve the efficacy of treatment.
  • We are investigating the host immune response to both the virus and the tumour in order to maximise the potential of our viruses to boost anti-tumour immunity.
  • Studies at the BCI also involve the determination of how genetic alterations in the tumour modulate viral potency and how the viruses interact with current therapies.
  • We are identifying predictive biomarkers for virus activity in tumour cells and exploring how the inflammatory response to viral infection can be modified to augment virus-induced cell death.

Key Publications

  • Connell et al. Genomic DNA damage and ATR-Chk1 signaling determine oncolytic adenoviral efficacy in human ovarian cancer cells. J Clin Invest. 2011; 121: 1283-97.
  • Wong et al. Modification of the Early Gene Enhancer-promoter Improves the Oncolytic Potency of Adenovirus 11. Molecular Therapy 2011; Nov 15. doi: 10.1038/mt.2011.242. [Epub ahead of print]
  • Cherubini et al. The oncolytic adenovirus AdΔΔ enhances selective cancer cell killing in combination with DNA-damaging drugs in pancreatic cancer models. Gene Ther. 2011; Oct 6. doi: 10.1038/gt.2011.141. [Epub ahead of print]
  • Hiley et al. Lister strain vaccinia virus, a potential therapeutic vector targeting hypoxic tumours. Gene Therapy 2010; 17: 281-7.
  • Oberg et al. Improved potency and selectivity of an oncolytic E1ACR2 and E1B19K deleted adenoviral mutant in prostate and pancreatic cancers. Clin Cancer Res. 2010; 16: 1845-55.
  • Wang et al. CEACAM6 attenuates adenovirus infection by antagonizing viral trafficking in cancer cells. J Clin Invest. 2009; 119: 1604-15.
  • Baird et al. Oncolytic adenoviral mutants induce a novel mode of programmed cell death in ovarian cancer. Oncogene 2008; 15: 3081-90.
  • Wang et al. E3 gene manipulations affect oncolytic adenovirus activity in immunocompetent tumor models. Nat Biotechnol 2003; 21: 1328-35.

Who does the research

→ Click here for BCI senior researchers working on cancer gene therapy.

Major Funders

  • Cancer Research UK
  • MRC
  • Pancreatic Cancer Research Fund
  • Pancreatic Cancer UK