Crusade Laboratories Ltd
Winner of SMART Award
"Crusade Laboratories, a Scottish biotechnology company with its roots in a Scottish university is at the forefront of biotherapy for cancer. SMART Awards have allowed us to maintain our advantage."
The Way They Were
Moira Brown was Professor of Neurovirology at the University of Glasgow until April 2003 when she decided to be employed full-time by her company, Crusade Laboratories Ltd.
She has pioneered the use of herpes simplex virus (HSV) as a therapeutic for cancer and has been instrumental in demonstrating that basic academic research in the life sciences can be translated from the bench to the patient.
The academic team led by Professor Brown was responsible for showing that the common cold sore virus, herpes simplex can be disabled in such a way that it is no longer able to destroy the cells of the brain and cause encephalitis. In addition, they were able to show that this modified virus could only replicate in actively dividing cells and not in the normal fully differentiated cells of the body.
This discovery of avirulence coupled to selective replication competence only in actively dividing cells, highlighted to Professor Brown that the modified virus HSV1716 may have a role in treating cancer.
Following intense preclinical research, HSV1716 was injected into the tumours of patients with the intractable brain cancer, glioma. After permission from the Department of Health, Gene Therapy Advisory Committee (GTAC) and the Medicines Control Agency (MCA), the first patient was treated in October 1997 and this was a world first.
The portfolio of IP attached to the virus and its application became the backbone for Crusade Laboratories Ltd which was formed in December 1999. By that time, a considerable number of patients had been treated and no toxicity had been experienced by any patient.
Using the SMART Award
The clinical results gave credence to the potential of HSV1716 as a cancer therapeutic. Building on this strength, Professor Brown decided that not only could the virus be a cancer killing agent in its own right but that it could be used as a vector to deliver other cancer killing products.
To take this research forward, the company needed extra support in the form of staff and consumables and thus Crusade Laboratories applied for, and were successful in obtaining, a SMART:SCOTLAND Award.
The first part of the SMART Award allowed Crusade Laboratories to modify the prototype virus HSV1716 to express an enzyme, nitroreductase. This enzyme is used to activate a compound CB1954 which on activation becomes a cell-killing chemical. The concept is called GDEPT - gene directed enzyme prodrug therapy and it is a form of targeted chemotherapy.
The SMART Award has allowed the combination of oncolytic virus therapy with targeted chemotherapy in the form of a 'magic bullet'. By injecting the new virus directly into tumours, the tumour can be killed both by the virus and by the chemotherapy. The distressing side effects associated with normal chemotherapy are avoided because CB1954 only becomes toxic where nitroreductase is expressed, i.e. in the tumour and not in other organs in the body.
The laboratory results have shown that tumour cells infected with the new virus and treated with CB1954 are killed more effectively than tumour cells infected with either HSV1716 or CB1954 alone. The concept has been proven that Crusade's prototype virus can be used to deliver targeted chemotherapy effectively.
The success of the first Award allowed the company to obtain Part 2 of the SMART Award to take the new virus into preclinical studies in models of glioma, melanoma and ovarian cancer. This part of the project started in September 2003 and is making good progress.
The Effect of the SMART Award
Professor Brown said:
"Crusade Laboratories, a Scottish biotechnology company with its roots in a Scottish university, is at the forefront worldwide of biotherapy for cancer.
"SMART Awards have allowed us to maintain our advantage. Our company is based on many years of basic academic research; a belief that we have discovered an effective therapy for cancer; a determination to translate from the "bench to the patient" and a fundamental belief that there is a basic obligation to give back to society and to make sure that ideas and innovation have the best chance of exploitation.
"The Scottish Government has helped in this achievement. There is a long way still to go to get a registered, marketable product and we continue to push forward with determination and belief in our technology."
At the end of 2003, >50 glioma patients, 25 patients with squamous cell carcinoma of the head and neck and 5 patients with melanoma had been treated in Phase 1 toxicity trials with HSV1716. The results have been highly encouraging and a European multi-centre efficacy trial in glioma patients is due to start in 2004. The European Medicines Evaluation Agency (EEA) has recently awarded Crusade 'Orphan Drug' status for its lead product HSV1716.
Contact Details
Crusade Laboratories Ltd
PO Box 1716
Glasgow
G51 4WF
Contact: Professor Moira Brown
Director
Tel: 0141 445 1716
Fax: 0141 445 1715
Email:
smbrown@crusadelabs.co.uk
Website:
www.crusadelabs.co.uk
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