Austin, Prima happy after cancer therapy trial

A cell-based cancer therapy developed by the Austin Research Institute and Prima Biomed subsidiary company Cancer Vac has passed through Phase I clinical trials with no signs of significant treatment related side effects.

Ten patients were treated in the clinical trial, which was performed at the Austin Research Institute and the Austin and Repatriation Medical Centre in Melbourne.

Prima CEO Marcus Clark said the result was a significant milestone for the cancer immunotherapy program. "We believe it is a very important stepping stone towards bringing the technology to the clinic and into commercialisation," he said.

The cell based immunotherapy procedure is the result of about 10 years of research, according to ARI director Prof Ian McKenzie, who led the project. "For some years we've been trying to immunise patients against their cancer, and we've injected over 100 patients and not got the type of immune response that we want," he explained.

While injecting the vaccine directly into animals seemed to promote the correct immune response, this did not happen in the early human studies. "There are several reasons for this, but one of the major reasons is that the patients are suppressed, their body has allowed the cancer to appear and if you inject them, they really don't do terribly well at making an immune response," McKenzie said.

"So if we take it out of the body, we have a much greater chance of getting an immune response -- in fact, the way we're going now, a 100 per cent chance of an immune response versus a 20 per cent chance in the past."

The procedure to overcome this problem was developed by ARI scientists Prof Bruce Loveland and Dr Vasso Apostolopoulos.

McKenzie explained that the immunisation therapy used the patients' own cells which were obtained by apheresis, a process that removes white blood cells from the peripheral blood. The cells were then cultured in conditions that favoured the growth of dendritic cells for five days before being stimulated with the Cancer Vac product, which is known as Mannan Fusion Protein (M-FP).

M-FP consists of an antigenic portion of the Mucin-1 (MUC1) protein, which is over-expressed on several cancers, fused to mannan, a sugar which acts to enhance the immune response and production of cytotoxic or killer T cells.

The activated dendritic cells were then injected back into the patient. In this trial, each patient received three treatments over a 12-week period. The patients were monitored for side-effects and to examine the resulting immune response, especially the production of cytotoxic or killer T cells with specific anti-cancer activity.

Desired immune response

"Surprisingly, all of our patients made an immune response, 10 out of 10," McKenzie said. "Now 10 out of 10 is not 100 out of 100, but we have to do this to get to the next stage and all our patients made the desired immune response.

"This is quite remarkable. What we've done by taking this out of the body is overcome the difficulty or inability of patients to make their immune system recognise the cancer, and there are no side-effects whatsoever."

The next step for the scientists, he said, would be to make the procedure a bit more user friendly. One way of doing this would be to freeze the activated dendritic cells, so that the patients only have to undergo one apheresis procedure. They also want to look at longer term treatments.

These will be evaluated in an extension to the Phase I study, according to McKenzie, but Prima/Cancer Vac is also planning a Phase II efficacy study, to begin early in 2003. This study will involve about 40 patients. "We're going to assess the clinical benefits in a more regular way than we've been able to do in the Phase I study and will hopefully get data within a year of the study starting," he said.

In addition, the researchers are continuing to develop other antigens suitable for use in the cancer vaccine program. "My own feeling is that a cocktail of many antigens would ultimately be better," McKenzie said.

One advantage of the cell based therapy is its potential for a short time to market, particularly in Australia and Europe, according to Clark. This is because the product is not a drug, but a blood product, and thus goes through a different, shorter regulatory process with the TGA in Australia and equivalent agencies in Europe.

"In Australia, the opportunity exists for us to market and distribute the stimulant and procedure ourselves," said Clark. He said that the therapy could be on the market in as little as three to five years after Phase II studies, and Prima is already initiating talks with major Australian hospitals regarding the infrastructure required for the therapy.

According to Clark, the plan is for the company to handle the product in Australia, as the market is small, and mainly restricted to the big teaching hospitals in the capital cities. The company is already engaged in preliminary discussions with a number of US companies, including Dendreon, which has its own cancer vaccine technology, and Progenitor Cell Therapy, a company set up to commercialise cell therapies. Japan is also a potentially huge market as cytotoxic therapies are not popular there.

"We would prefer to go with companies with experience in cell based therapies," Clark said. He said that partnering would probably happen on a country-by-country basis, given the need for close relationships with oncology centres.