First Steps Towards A Vaccine For Pancreatic Cancer

Dr Robert Maki told ECCO12 – The European Cancer Conference - today (Monday 22 September) that preliminary work with a cancer vaccine created from a heat-shock protein¹ taken from the patient's own tumour had resulted in one patient out of the ten vaccinated still alive and without disease after five years, and two more alive and without disease after more than two years. The typical survival after surgery for pancreas cancer is 14-15 months.

However, Dr Maki warned that patients should not get excited about the results of this research as it was too early to tell whether it would be possible to create a vaccine that could be used on all pancreatic cancer patients, and the patients involved in the trial had been carefully selected and might have been ones that would have done well anyway.

Dr Maki, an assistant member in the division of GI oncology in the department of medicine, and co-director of the sarcoma programme at the Memorial Sloan-Kettering Cancer Center in New York, USA, told delegates that he and his colleagues had run a phase I trial on 10 pancreatic patients using a vaccine based on a heat-shock protein called HSPPC-96 taken from the tumour of each patient (i.e. autologous).

Initial problems in creating the vaccine meant that the study was delayed half way through the study to improve the vaccine-making process. Dr Maki said: "The problem is that the pancreas makes digestive enzymes that destroy proteins . . . in other words, the pancreatic tumour cells themselves can destroy the vaccine you are trying to make, if you do not handle the tumour tissue carefully and quickly. With improvement in the vaccine purification process, most patients with the primary pancreatic cancer enrolled on the study were able to receive vaccinations."

First, surgeons operated to remove completely the primary tumour, and then the patients were vaccinated within eight weeks of surgery. As far as doctors could tell, the patients were disease-free at the time of their vaccinations. None of the patients suffered side effects that limited the dose of the vaccine, and none had chemotherapy or radiotherapy.

Dr Maki said: "Tests on the patients showed that at least some people we examined made a response against the vaccine and therefore, hopefully, against the cancer. However, we will only get a better picture of the efficacy of this vaccine when we have the clinical results from a larger study." The overall survival for the 10 patients was two and a half years, in comparison to 14.3 months, the historical average.

"Over 95% of people with pancreatic cancer die, typically within two years of diagnosis, and mortality is still about 90% even for those who have complete removal of their pancreatic cancer. So the finding of even a few patients surviving two years or more is promising regarding the usefulness of this vaccine after removal of the cancer. However, and this is a big however, we may be biased in who we selected for the study. Only people who could have an operation were eligible; we screened out people who had evidence of spread of tumor before they entered the study. Perhaps, just by chance, we got a few people who were destined to do well. So enthusiasm about any phase II study has to be tempered by the fact that you need a proper randomized study to determine the vaccine's usefulness," he said.

HSPPC-96 has been shown to have quite a dramatic effect in some patients with metastatic melanoma and so Dr Maki hopes that trials could be run to further test its efficacy against pancreatic cancer as well. In the meantime, until a larger study has been run, it will not be known for certain whether this vaccine has real potential against pancreatic cancer. Trials are also underway to test the vaccine in the treatment of kidney cancer.

The story of this vaccine is a good example of how earlier discoveries at the lab bench can eventually translate into potential new therapies for patients. Dr Maki's PhD was based on cloning and purifying the human HSPCC-96 molecule. "It is nice to see that well over 10 years after my PhD, this interesting molecule is undergoing examination in the clinic. It is gratifying to see the studies move from the bench to patients, where I hope some benefit will be seen. Similarly, this same technique could be used in preparing vaccines against infectious diseases – another very large area of potential use for these vaccines."

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Note:

¹ Heat-shock proteins (HSPs) are made by genes in response to some form of stress on a cell and help the cell rebuild itself after a potentially lethal attack. HSPs work by sticking to and refolding damaged proteins back to their normal structure. A tumour cell would have HSPs stuck to proteins specific for the cancer, and a vaccine based on HSPs taken from the patient's tumour would prompt the patient's immune system to attack cells containing the proteins stuck to the HSPs wherever they were – the greatest number of that particular type of proteins being in the tumour itself – thereby killing the cancer.