Wednesday, February 12, 2014

Autologous vaccines for treatment of cancer in dogs - and guinea pig update

Dr Weir's pomeranian Tex hangs twenty on a surfboard at home. As you do.
UPDATE: Chris and his team have just published an article on the use of streptavidin as a novel immunostimulant for delivery of autologous vaccines in Cancer Immunology Research. See here.

Immunotherapy is a hot area of oncology research, but it isn't easy to get one's head around. As SAT readers will know we're undertaking an oncology distance education program this year, and so far a structured investigation into the literature on cancer in companion animals has been mind-blowing.

Tumour cells survive in part by evading the immune system, so turning the immune system against tumours makes intuitive sense. Of course, tumours are heterogenous, complex structures and there is no magic bullet. They can maniupulate the immune system and use things like inflammation to their advantage. However, canine trials of autologous vaccines are promising.

WARNING: There is a surgical image in this post of a spleen. The patient is anaesthetised and the spleen was removed without complications, and the patient made a full recovery. Spleens look like big purple things and in the scheme of things they aren't all all disgusting, but some readers might want to scroll down with care.

Dr Christopher Weir, at the Bill Walsh Translational Cancer Research Laboratory at Sydney’s Kolling Institute, has been involved in the development of vaccines which have the potential to improve life expectancy of both human and animal patients with cancer.

He uses cells from the dog's own tumour as source material to create an individualised vaccine. In preliminary trials the vaccines have successfully slowed the growth of tumours, reduced the incidence of new tumour formation and prolonged the lives of canine patients, some of whom were diagnosed with advanced cancer. SAT had the opportunity to ask Dr Weir some questions about his research.

How did you get involved?

It started about eight or nine years ago. My then boss Professor Ross Davey was interested in targeting vasculature proteins of tumours with either drugs or monoclonal antibodies carrying drugs. We had developed a method where we could isolate proteins from the vasculature of tumours, and spent about a year trying to make antibodies against these proteins.

It dawned on me that we could see if they would work in a vaccine scenario. We started with pretty crude vaccines around four to five years ago that didn’t work initially. Since then we’ve done a lot of work to improve and then fine-tune them.

How do vaccines work against cancer?

We aim to get as much of the tumour as we can, and we mash it up, using soluble proteins in a special buffer. We slightly modify the tumour proteins and link these to a bacterial protein, which acts like a stimulant and attracts T-cells. Our understanding is that because the tumour cells are linked to a stimulant, the immune system processes and recognises them as foreign, then goes back in and attacks the residual tumour.

But the sample needs to be large?

Where we only have a biopsy sample it doesn’t work as well. We think that you need to disrupt the tumour significantly because it is a closed off environment. The immune system gets in there but its effects appear to be short-lived. If you get a nice chunk and disrupt the tumour, and then vaccinate, the immune system has a bit of an advantage. We’ve made vaccines for dogs with really advanced cancer, and their vets have done some pretty amazing surgery to get a good part of that tumour out.

Splenic mass being removed via an emergency splenectomy. (NB this mass turned out to be a haematoma, not a tumour, but one needs histopathology to differentiate).
How long does it take to make the vaccine?

Dependant upon when the sample is received, the vaccine should be ready for injection at the vet by suture removal. The tissue needs to be fresh or frozen – you can’t have formalin near it.

How many vaccines does a dog need?

Two shots, three weeks apart.

Would autologous vaccines work against some cancers better than others?

It seems so, although it may be too early to tell. For the safety trial we have taken on almost any patient whose owners are willing to enrol them in the study. One type of cancer the vaccines work particularly well on is osteosarcoma. The average survival time with amputation and chemotherapy is around 9-12 months. We’ve treated three dogs with vaccines, and two lived beyond two years. The third had metastatic disease and lived for nine months.

Are you still accepting animals into the trial?

We have limited places left in the safety trial and we only have Animal Ethics approval for cases in NSW, Queensland or Victoria. As a part of this trial the Bill Walsh Cancer Research Laboratories have made the vaccines for free but we do require the tumour to have histopathology done on it to be correctly identified and graded, and be able to track the dog’s progress.

RegeneusLtd have the rights to commercialise the vaccine and next year we will perform a controlled study on the use of the vaccine in dogs with osteosarcoma in the US.

What about cats?

We haven’t yet obtained ethics approval to recruit cats.

Dr Weir will be talking at the 2014 Annual AVA Conference in Perth. For more info visit the conference website here.

Meanwhile, about those guinea pigs...

I've had a lot of queries about the wellbeing of Osler and Cushing, the guinea pigs born on Saturday. I can report that they continue to be the cutest critters on the planet, they're healthy, and that Cornflake really is the most wonderful mother. If you have the opportunity, now is the time to buy shares in Basil, bok choy, parsley and every other vegetable that I am spending a fortune on. Cornflake is making up for all the calories she pumped into those babies!!! 
Cushing and Osler are held while their Orchard grass is freshened up.