First European trial for new breast cancer vaccine

European clinical trials are under way in Denmark and the UK testing a new breast cancer vaccine targeted against the HER-2 growth factor.

HER-2 is overexpressed in about a quarter of all breast cancers and has become a key target for new treatments, such as the monoclonal antibody therapy Herceptin.

But, the development of a vaccine by Danish pharmaceutical company Pharmexa represents an entirely novel treatment paradigm, according to Pharmexa’s manager of preclinical development and immunopharmacology, Dr Dana Leach.

He told a news briefing at the 3rd European Breast Cancer Conference in Barcelona: “The objective of our vaccine is to stimulate the patient’s own immune system and to see whether we can induce it to launch specific killer cells as well as producing HER-2 specific antibodies. This is a phase I/II trial. Our first objective is to test the safety of the vaccine, but we also want to make a preliminary evaluation of the vaccine’s ability to raise an immune response. There are 27 patients with advanced breast cancer in the trial, which should be completed late this year.”

HER-2 is a protein that is overexpressed in many tumours. But, because it is also expressed at low levels in some normal tissues, the immune system does not recognise it as foreign and the immune cells, especially helper T cells that initiate the immune response, are simply not around to launch an attack. So, the vaccine – AutoVac – has been designed to help kick-start the immune response by giving the T cells a foreign agent to recognise and react against. The aim is that the immune system then recognises the overexpressed HER-2 in the cancer cells and attacks them, but ignores the normal tissue because that contains only low levels.

Dr Leach said that animal tests had shown that the vaccine produced a specific immune response and there had been no adverse side effects.

The vaccine consists of two small inactive fragments derived from tetanus toxin – the bacterium that causes lockjaw. The researchers included DNA encoding the fragments, into DNA that they had made in the laboratory to code for a portion of the HER-2 molecule. The DNA vaccine is injected and taken up by the cells, which then manufacture the protein, including the inserted tetanus fragments that ‘wake up’ the immune system and help it to respond to HER-2.

Dr Leach said the company was also preparing to start clinical trials in a variation of this approach. Instead of a DNA vaccine that prompts the body’s cells to make the necessary protein, the AutoVac protein will be made beforehand in the laboratory and injected directly as a vaccine into the patient.

“Each approach has potential advantages – DNA is generally believed to be a good way to get a response from cytotoxic T cells, while protein is better at inducing antibody responses,” he said. “We have to look at tackling cancer from as many different approaches as possible because different tumours react in different ways. We know that already from the variable responses to chemotherapy, radiotherapy, endocrine treatment and other immunotherapies. But, as we get better at diagnosis and understanding the genetic make-up of tumours it should become possible to make better predictions about which treatment is best for which patient and to combine treatments that work synergistically to boost effectiveness.”

Dr Leach said that the success of the drug Herceptin as a treatment had shown that HER-2 was a good target. “Although it is early days yet, any time that you can successfully take a new cancer vaccine into the clinic it is an important and exciting event.”