It builds on previous research showing the vaccine, known as AE37, to safely and effectively raise immunity against human epidermal growth factor receptor 2 (HER2) – an oncoprotein that promotes tumour growth and is expressed to some extent in 75-80 per cent of breast cancer tumours.
The researchers found that patients who received the vaccination had an estimated recurrence rate of 10.3 per cent compared to 18 per cent in the control group at a median follow up of 22 months. This represented a 43 per cent reduction in the risk of recurrence.
"The vaccine educates the immune system to recognise HER2 as an invader," said Doctor Elizabeth Mittendorf. "By introducing it into women who have had breast cancer, our goal is to instruct the immune system to immediately recognise any recurring cancer cells and orchestrate an attack."
The AE37 peptide vaccine used in this study is a hybrid modified to increase its potency in generating an immune response specific to cancer cells expressing HER2. It consists of a fragment of the HER2 protein (AE36), a MHC Class II epitope, linked to an Ii-Key peptide. Together, they work to stimulate a robust CD4+ T cell response, prompting the components of the immune system to seek and destroy tumour cells.
To help T cells better recognise AE37, researchers also paired the vaccine with an immune stimulant known as granulocyte/macrophage colony stimulating factor (GM-CSF). The vaccine is injected under the skin similar to a tetanus shot. The initial series consists of inoculations given monthly for six months followed by four cycles of boosters every six months.
Most experimental drugs are first evaluated in patients with metastatic disease, when tumours have undergone drastic changes, including immunoescape – a mechanism that allows tumour cells to evade elimination by the immune system. "There is very little chance a single peptide vaccine like AE37 will overcome a tumour at this stage of disease," said Mittendorf. "For this reason, it is more realistic to use the vaccine to prevent recurrence rather than to treat a large mass of already present cancer cells."
He added: "This is an exciting time for immunotherapy as we transfer knowledge from the lab to clinic. There is a renewed enthusiasm to manipulate the immune system therapeutically – from vaccines and antibodies to combining these modalities and improving response rates."
MEDICA.de; Source: The University of Texas