Professor Moira Brown and beating brain cancer with a herpes virus
A team lead by Professor Moira Brown from Glasgow’s Southern General Hospital has produced promising Clinical Trial results using a virus to selectively kill cancer cells in real-life patients with brain tumours. We first covered her work at CANCERactive some 8 years ago. This alternative cancer treatment is often called virotherapy.
What is virotherapy? It is the use of common viruses either acting on their own because they are known to replicate strongly inside cancer cells and thus kill them (while healthy cells fight them off), or, in some cases, the viruses have been used as mutated carriers, made harmless so that they can carry a cancer killer into the tumour. For more detailed examples see HERE.
First, Professor Brown had to persuade a hospital ethical committee to allow a virus to be given to terminally ill patients. In this case it was the herpes virus – the common cold sore virus.
As early as 2001, Professor Brown first noted in the laboratory that the herpes virus would multiply rapidly in a cancer cell, ultimately killing it. Moira Brown is, in fact, a neuro-scientist and this prompted her interest in using the herpes virus with brain cancer.
’We began our original phase-one trials in October, 1997 on seriously ill patients with three to four month’s life expectancy. We were initially looking to see if it was safe - if we could inject herpes into the brain and not kill the patient.’
In 2010, Professor Brown received the go-ahead to start full clinical trials. Again, the patients all had brain cancer. ’We decided to start treating one of the most intractable brain cancers, glioma, which has an average survival rate of one year following diagnosis,’ she says.
The patients received their injections during an operation called stereotaxic surgery: a hole is made in the skull and the virus is injected into the tumour.
The virus didn’t kill the patients and four of the patients were alive 18 to 30 months after treatment started. One patient is still alive nearly four years after commencing treatment. Scans of the patients’ tumours, which had previously been growing at a rapid rate, showed growth had been arrested by the virus.
’We were extremely encouraged by the results and are carrying out more trials on glioma patients,’ says Professor Brown.
As is the norm in Britain, full approval could be 5 years away. This is not the case in the USA where often, after promising initial results, patients are treated as part of an ongoing trial while approval is awaited. Professor Brown has been inundated with requests from patients to go on her trial. ’We have a limited number of patients to whom we can offer treatment. It is very sad because the outlook for gliomas is poor’, says Brown.
Meanwhile’ Brown is working on a new form of the virus which is expected to have greater cancer-killing powers. If the current brain cancer research finishes as a success, she will move to phase III studies in two years.
Interestingly, doctors believe this particular virus will work against many common cancers, including ovarian, prostate and lung cancers.
Virotherapy has been around for nearly 20 years. We have covered the story of two lung cancer patients alive more than a dozen years after trials at MD Anderson in Texas. Viruses like the herpes virus can be genetically modified so they only attack and multiply inside cancer cells.
In America Cedars-Sinai and the Mayo Clinic are in the forefront of this work. Researchers at the Mayo Clinic have tested the use of the Measles virus with gliomas. “We are looking at better ways to treat some of the most lethal cancers”, said Dr. Eva Galanis, leader of the project. Dr. Galanis and her co-investigators discovered that a vaccine strain of the virus causes glioma cells to fuse, forming multinuclear cell aggregates that trigger cancer cell death. In both laboratory work and in several animal models measles virus strains have been shown to significantly shrink glioma tumors and prolong animal survival (1)
In April 2009, the U.K. based Ark Therapeutics released an update on promising results from a multi-center Phase III clinical trial using a ‘first-generation adenoviral vector encoding TK’ called Cerepro (2). Unfortunately, the European Medicines Agency (EMEA) rejected Ark Therapeutics’ marketing application after deciding that the study was statistically underpowered and failed to show sufficient efficacy in terms of postponing death or re-intervention. The decision by the EMEA is currently under appeal by Ark Therapeutics.
Ref:
(1) The Mayo Clinic; http://www.mayoclinic.org/medicalprofs/measles-virus-glioblastoma-therapy-nu0901.html–
(2) Ark Therapeutics, 2009; Osborne, 2008.