Download Transcriptional targeting of replicating adenoviruses for cancer gene

Transcriptional targeting of replicating adenoviruses for cancer gene therapy: non-GMP costs
Many defects in tumour cells are now known at the molecular level. This makes it possible to
devise rational strategies for targeting tumour cells without harming normal cells. This usually
requires introduction of exogenous DNA into tumour cells, and the most efficient way to do
this is with viruses. Unfortunately, the amount of virus which can injected is never enough to
infect all of the tumour cells. To get around this problem, we are developing adenoviruses that
replicate selectively in tumour cells. In principle, these viruses will replicate and produce more
virus until all of the tumour cells are destroyed. A virus of this type is currently in clinical
trials for prostate cancer in the US. We are trying to develop a similar virus for colon cancer.
If successful, we plan to use it to treat liver metastases from colorectal tumours.
Colon cancer is a leading cause of death in the developed world. In many cases surgical
treatment of the primary tumour can cure local disease affecting the colon, but the patient is
left with tumour metastases. Unlike, for example, breast cancer, these metastases are normally
concentrated in the liver. This occurs because the venous blood from the colon is filtered by
the liver before entering the general circulation. Successful treatment of liver metastases
would significantly improve the survival of patients with colon cancer.
Gene therapy for cancer is in its infancy. What is required is a virus which is highly toxic to
tumour cells but does not harm normal cells. If the virus is too effective but not sufficiently
selective there is an obvious risk of creating a new pathogen. Hence the field is progressing
slowly and the current vectors are all based on relatively innocuous viruses. It is unrealistic to
expect miracle cures from these viruses. The challenge is to identify a situation where these
viruses could, despite their relatively low efficacy, produce a clinical benefit.
Injection of large amounts of virus directly into tumours has been shown to kill tumour cells
and produce local responses, but purely local treatment adds little to the existing range of
treatments for cancer. We believe that liver metastasis from colon tumours is a situation where
a gene therapy approach could bring something new. This is because the disease is limited to a
single organ, the liver, which can be treated with a high local dose of virus by injecting the
virus into the hepatic artery.
Reference:
IGGO, Richard
ISREC, Chemin des Bovéresses 155, CH-1066 Epalinges tel 021 692
5889; 021 652 6933 e-mail: [email protected]
Title:
Transcriptional targeting of replicating adenoviruses for cancer gene
therapy: non-GMP costs
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