New keys found for unlocking head and neck cancer treatment

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QIMR Berghofer scientists say the discovery of new cellular immunotherapy targets for a deadly type of head and neck cancer, caused by human papillomavirus (HPV), could lead to better survival rates.

The research findings will be published Tuesday 28 July in the Journal of Experimental Medicine.

The type of head and neck cancer, known as oropharyngeal cancer, can affect the base of the tongue, the tonsils, soft palate and the walls of the pharynx. HPV is detected as the cause of almost 50 per cent of oropharyngeal cancers in Australia.

Cellular immunotherapies, which harness the human immune system to fight disease, have had limited success in treating HPV-induced cancers, including oropharyngeal, cervical and ano-genital cancers.

Lead researcher and the head of QIMR Berghofer’s Centre for Immunotherapy and Vaccine Development, Professor Rajiv Khanna AO, said the team uncovered additional targets, which will allow them to develop more effective cellular immunotherapies.

“It is only when specific proteins on the surface of our immune cells recognise specific proteins on the surface of the virus-infected cancer cells that the immune cells can destroy the cancer and stop it from growing,” Professor Khanna said.

“Up until now, it was believed that our immune cells only recognised and reacted to two particular proteins – known as E6 and E7 – expressed in HPV-positive cancer cells.

“The immunotherapies developed to date to treat HPV-associated oropharyngeal cancer have targeted these E6 and E7 proteins, but that hasn’t proven very effective for HPVassociated oropharyngeal cancer.”

Professor Khanna and his team conducted an in-depth analysis of immune cells, known as T-cells, taken from 66 oropharyngeal cancer patients recruited from the Royal Brisbane and Women’s Hospital and the Princess Alexandra Hospital.

“Contrary to what has previously been believed, we found that T-cells are also capable of recognising four other HPV proteins expressed in cancer cells,” Professor Khanna said.

“We are now developing lab-engineered killer T-cells that were trained to target all six HPV proteins to open up the defences of the virus-infected tumour cells and kill them off. We believe that attacking multiple HPV proteins will work better than just targeting two.”

Co-lead author and Director of Radiation Oncology Research at the Princess Alexandra Hospital in Brisbane, Professor Sandro Porceddu said the findings will make a significant contribution to understanding this disease and help doctors refine treatments through future clinical trials.

“We’re already working on developing better killer T-cell immunotherapies that recognise all, or a combination, of these proteins,” said Professor Porceddu who is also a researcher at The University of Queensland.

“It’s akin to a lock and key relationship. First we had to find which protein locks were stopping the immune cells from getting through to the cancer cells, and now we have to develop T cell immunotherapies in the lab that have the correct keys to open the locks.

“Different combinations of the proteins are present on different patients’ cancer cells, so we will develop immunotherapies with different bunches of keys for different patients.

“HPV-associated oropharyngeal cancer has increased significantly globally and in Australia.

Data from the Cancer Alliance Queensland shows it is the most common head and neck cancer in the state with the incidence rate increasing by 162 per cent in men and 40 per cent in women over a 15 year period.

“The increasing incidence and prevalence of this disease makes improving treatment outcomes, with the least amount of morbidity, paramount.”

The researchers hope to begin clinical trials of the new cellular immunotherapies in 12 to 18 months.

The immunotherapies for the clinical trial will be made at QIMR Berghofer’s Q-Gen Cell Therapeutics, which is one of the largest cell therapy manufacturing facilities in Australia.

The findings could also have implications for the immunotherapies used in other HPVassociated cancers.

The research involved collaborators at The University of Queensland, the Royal Brisbane and Women’s Hospital, the Princess Alexandra Hospital and Atara Biotherapeutics. It was funded by Atara Biotherapeutics and the National Health and Medical Research Council of Australia.
 


Quick Facts:

Cellular immunotherapies are developed by extracting T (immune) cells from a patient or donor’s blood and turbo-charging and training the immune cells to recognise and kill off disease.

Oropharyngeal cancers are the sixth most common type of cancer worldwide, and their incidence is growing.

According to the Australian Institute of Health and Welfare, The number of head and neck cancers diagnosed in Australia increased from 2,475 in 1982 to 3,896 in 2009, and it affects more men than women.

Despite the approval of two effective HPV vaccines, including the Queensland developed Gardasil vaccine, the effect of the vaccine in preventing oropharyngeal cancers isn’t expected to be evident for a number of decades.

 
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