By Chris Woollams
Virotherapy, or using viruses to kill cancer, is a fast emerging ’treatment of potential’ in the domain of ’alternative cancer therapies’. A new cancer treatmenty, some would say an alternative cancer treatment, that uses genetically modified common viruses (oncolytic viruses) to attack cancer cells, whilst doing little or no harm to healthy cells. And it is based on cutting edge work from the UK. Read this article from Cancer Watch in icon magazine to understand it a little more:
MD Anderson Celebrates Gene Therapy Success
Back in 1997, Dr Jack Roth of the MD Anderson Cancer Centre pioneered work using a genetically engineered virus, with human lung cancer patients. Five years on they are celebrating the results. Two patients (Alfredo Gonzalvo, now 78 and Bernis Teaters, now 84) became medical pioneers by having the treatment in conjunction with 6 weeks of radiotherapy. Roth used an adenovirus (the bug that causes the common cold) as a vector to take in healthy copies of the p53 gene, right into the lung cancer tumours. The therapy is currently on fast track FDA Approval.
The therapy has shrunk lung tumours in over half the patients trialled
The pioneering work started with a premise: The p53 gene, which normally acts to suppress uncontrolled cell growth, is missing or mutated in about 50 per cent of human cancers, and dysfunctional in the rest. So let’s get the p 53 gene back inside the tumour to regulate the cancer growth and normalise the cells.
The therapy, called Advexin, has shrunk lung tumours in over half the patients trialled. Both the above named patients were treated in May 1999, and are celebrating their fifth anniversary.
MD Anderson has run more than 20 trials to date, featuring 600 patients. Advexin has been used in lung, head and neck, breast and ovarian tumours, whilst other viruses have been tested with brain tumours and metastatic lung cancers.
The only hiccough to date has been a tendency for immune response in patients, but Roth is now using genes encased in liposomes which act like shrink-wrapping to get the active ingredient past the healthy cells and into the tumour.
The principle is simple. First find your virus, and then train it to specifically attack tumour cells. This ’training’ usually involves gene modification so that healthy cells can recognise it and destroy it leaving it only a problem for the cancer cells. There it could cause lysis and destroy the tumour, it could deliver therapeutic genes, or even specific anti-cancer drugs.
Such self-replicating viruses have already been tested both in vitro and in vivo. They can be used instead of radio and chemotherapy, or alongside it without affecting healthy cells.
They can be used without affecting healthy cells
Example 1: Daniel Meruelo (New York University School of Medicine) has undertaken pre-clinical trials and shown that Sindbis virus can target ovarian, kidney, stomach, colon and advanced pancreatic cancers (Nat Biotechnol 2004, 22: 70-77). To date Meruelo has done his tests with mice, but given the poor progress with pancreatic and ovarian cancers he hopes to begin human trials within 2-3 years.
Example 2: Darren Shafren (University of Newcastle NSW) showed that coxsackievirus A21 causes lysis and complete destruction of melanomas. He has undertaken this research in vitro and in mice. The CVA21 virus is an enterovirus; it causes the common cold. Just one injected dose directed into the tumours caused their destruction. The melanoma actually seems to cause rapid multiplication of the virus.
Work is taking place in the UK too. Again read this short piece from icon:
UK Gene Therapy Trial For Brain Tumours
Notwithstanding the MD Anderson work, Professor Norman Nevin, chair of the UK gene therapy committee believes the UK is at the forefront of their type of work. His committee has given the go-ahead for a team at Glasgow University, lead by Professor Moira Brown, to treat 100 patients with gliomas using a genetically modified form of the herpes virus.
In the normal brain, this virus can cause encephalitis. But this modified virus has a gene removed so that it leaves normal cells unharmed but replicates in a cancer cell, causing them to burst open, and spread the disease to other cancer cells.
39 patients have been involved in three previous trials. Currently orthodox medicine has no cure for gliomas. But one is still alive from a 1997 trial and five from a more recent trial. All greatly exceeded their doctor’s diagnosis, as did a number of other patients in the trial. Brown added that this was the most advanced gene therapy trial in the UK.
All greatly exceeded their doctor’s diagnosis, as did a number of other patients in the trial
There are a number of implications and questions that still need answers.
In the melanoma study, the virus multiplied and headed off around the body to other, distant tumours. All this on a very low initial viral dose. Where does the virus stop?
The mice used in the experiments all had immune deficiency - so that they didn’t kick out the virus. How will that translate into human therapy? Already the M D Anderson team are acknowledging that immune response is a problem and so they are coating - and thus hiding - their virus from healthy cells.
Will it work for late stage disease as well as it does for early stage? To what degree is the immune deficiency essential? And what are the side effects and risks?
So, early days yet, but researchers all over the world are working in this field using viruses like adenovirus, herpesvirus (on breast cancers) and poliovirus.