Fighting chance

PUBLISHED : Tuesday, 07 February, 2012, 12:00am
UPDATED : Tuesday, 07 February, 2012, 12:00am


He seemed to be doing everything right for a healthy life: he did not drink or smoke, and had been running and swimming every day for the past decade. But Lai, 46, a policeman, was diagnosed with first-stage nasopharyngeal cancer in 2006.

The next two months of radiotherapy went well, destroying all his cancer cells. But seeing people around him suffer a relapse after successful treatment, Lai is worried the cancer will strike again.

'A colleague of mine got his nasopharyngeal cancer successfully treated in 2006, but it spread to his lungs in 2011,' he says.

But recent advances in cancer vaccines provide hope for Lai and millions of other sufferers worldwide. Immunotherapy, in particular, holds promise. Oncology experts are manipulating cancer-causing viruses to develop vaccines that trigger the immune system to attack cancerous cells.

Globally, a host of cancer vaccines are in the pipeline. According to a University of Michigan Health System report published in November, the types of cancer with the highest number of active clinical trials worldwide last year were melanoma (40), breast (34), lung (30), prostate (22) and brain (20). Unlike common vaccines for diseases such as polio and measles, which are given to healthy people for lifelong immunity, these vaccines are for those already afflicted with cancer.

Professor Anthony Chan Tak-cheung, director of the Hong Kong Cancer Institute and the Sir Y.K. Pao Centre for Cancer at Chinese University, is at the forefront of research on using the Epstein-Barr virus (EBV) to treat nasopharyngeal cancer, which strikes 1,000 new victims every year in Hong Kong.

'EBV has been identified for more than 40 years. There are many investigations into its role in causing cancer, but not much has been done on the use of the virus itself as a therapeutic target,' Chan says. The University of Birmingham in Britain is also doing EBV research, but it's for a vaccine for various types of lymphoma, such as Hodgkin's disease.

Last year, Chan's team recruited 18 patients - including Lai - for the first phase of a clinical trial. All the patients had early-stage nasopharyngeal cancer that had yet to metastasise or spread to other parts of the body. They had completed radiotherapy and chemotherapy.

Antigens that swarm on the surface of EBV cells were extracted and put into the vaccine, which was then injected into the patient's body. The flood of antigens triggers the immune system to sound the alarm, rousing T-cells (a type of white blood cells that plays a central role in the body's immune system) to zoom in on the antigens and attack the tumour.

Each patient was given three vaccine shots - one every three weeks. 'With no serious side effects observed in the patients, the vaccine has been shown to be safe,' Chan says. Results of the clinical trial were presented at the American Society of Clinical Oncology's annual meeting in Chicago in June. Immunotherapy is almost an opposite approach to traditional cancer treatments such as chemotherapy and radiotherapy, which kill cancer cells but also weaken the immune system, Chan says.

An added advantage of cancer vaccines is they're mostly free of side effects, such as hair loss, mouth ulcers and skin rashes, which are often seen with traditional treatments.

A phase-two clinical trial by University of Strasbourg researchers in France, which was published in October in The Lancet Oncology, showed that combining standard platinum-based chemotherapy with the new cancer vaccine TG4010 enhances the effect of chemotherapy and slows down the progression of advanced non-small-cell-lung cancer, the most common type of lung cancer, compared with chemotherapy alone.

In another study last year, researchers at the National Cancer Institute in the US found that a vaccine with tumour-associated antigens slowed cancer disease progression by a few months in some of the 26 female study participants with metastatic breast or ovarian cancer.

Provenge, the first tumour vaccine approved by the US Food and Drug Administration in 2010 to treat prostate cancer, targets an antigen called prostatic acid phosphatase, which is found in about 95 per cent of prostate cancers. It was found to extend life in cancer patients for around four months with very few side effects.

Professor Tony Mok Shu-kam, a specialist in lung cancer treatment from Chinese University's clinical oncology department, says major breakthroughs have been seen in cancer vaccine research that involve an antigen known as MAGE-A3, which occurs in 30 per cent to 40 per cent of lung cancer cases. 'The vaccine is under investigation,' he says. 'About 2,200 patients with early-stage lung cancer are randomised to receive the vaccine or a placebo after chemotherapy or standard surgeries.'

Chan has just begun the second phase of his research, recruiting patients with metastatic nasopharyngeal cancer - stage-two cancer that has spread to other organs such as the lungs and liver - to see whether the vaccine is effective in shrinking the cancer.

He says more than 90 per cent of nasopharyngeal cancer patients, including those at very advanced stages, can have their primary tumours eradicated after about two to three months of traditional treatments such as chemotherapy and radiotherapy.

But two to three years later, 30 per cent of these patients will relapse, with the cancer spreading to other parts of the body.

'Treatment for metastatic disease is palliative in nature, and in general it's impossible to cure the disease at this stage,' Chan says. 'Metastasis in such cases is caused by residual cancer cells.

'The reason for metastasis to afflict the 30 per cent of patients while sparing the 70 per cent must have something to do with the immune system.'

The University of Hong Kong's faculty of medicine, working with the Queensland Institute of Medical Research in Australia, is also researching immunotherapy for nasopharyngeal cancer. Called adoptive immunotherapy, it involves harvesting T-cells from a patient's blood and exposing them in vitro to EBV antigens that have been linked together to form polyepitopes. (An epitope is the part of an antigen that is recognised by the immune system.)

The T-cells are then injected back into the patient to trigger the body's immune response. Between August 2008 and April 2010, 14 metastatic patients with stage-four cancer received the T-cell injections once every two weeks. A total of three to eight vials of T-cells were administered.

The patients survived for an average of 17 months after treatment, compared with 10 months for other nasopharyngeal cancer patients in similar condition and treated during the same period by the university.

John Nicholls, clinical professor with HKU's department of pathology, says this type of immunotherapy was first used overseas in the early 2000s for a tumour associated with EBV that afflicts bone marrow or liver transplant patients - but HKU is the first to use it for nasopharyngeal cancer.

How long until a vaccine is developed? Chan declines to give a time frame, saying it depends on many factors. But history shows that it usually takes at least eight years for a cancer drug to go through four stages of clinical trials before it is approved by the government for treatment.

Not all cancers are caused by viruses, but those that are tend to present a window of opportunity for researchers, says Professor Dora Kwong Lai-wan, head of HKU's clinical oncology department. Apart from nasopharyngeal cancer and lymphoma, these include liver cancer and cervical cancer.

With the cervical cancer vaccine now used to prevent human papillomavirus infection among young women, she says scientists are tinkering with the concept of a preventative EBV vaccine, although there are no clinical trials yet.

Mok says vaccine treatment is still experimental. But large tumours are unlikely to respond to vaccines because of their sheer size. 'There is only so much killing the immune system can do,' he says.

But there's no doubt this is an exciting time for immunotherapy research. Says Kwong: 'It opens new doorways, allowing us to see whether we can fight cancer by strengthening our own immunity.'


(clinical trials worldwide in 2011)

- 40 melanoma

- 34 breast cancer

- 30 lung cancer

- 22 prostate cancer