Malaysians developing world’s first oral cancer vaccine

oral-cancerKUALA LUMPUR: Cancer Research Malaysia’s (CRM) laboratory in Subang Jaya, Selangor is nothing like the sleek and sophisticated-looking research facilities in Hollywood movies.

In fact, CRM’s lab looks thoroughly well-used, with scientists and research staff, in their ubiquitous long, white coats, walking about briskly and tables cluttered with papers, test tubes and microscopes.

While on a brief tour of the lab, Bernama was introduced to a quick “How to Create a Cancer Vaccine for Dummies” course, conducted by CRM’s Cancer Immunotherapy Programme team leader Dr Lim Kue Peng.

“So you guys literally cause cancer?” this reporter asked in jest, when told that CRM actually “breeds” oral cancer cells in the lab and provides them to research institutions around the world to study the gene function and to develop and test new drugs for oral cancer treatment.

Lim, the recipient of the L’Oreal for Women in Science Award 2016, merely smiled wryly in response. She was part of the CRM team that recently discovered an oral cancer specific antigen called MAGED4B, that cleared a significant path to the development of a vaccine to cure the cancer.

“It was like looking for a typo error in a three-billion alphabet sequence,” Lim, 40, remarked with regard to the finding.

The decade-long research by CRM’s Head and Neck Cancer Research team, led by Dr Cheong Sok Ching, has brought them on the verge of producing the world’s first vaccine for oral cancer.

Up to 4.1 million oral cancer patients worldwide are expected to benefit from this vaccine but prior to that, the team has to complete its pre-clinical studies and secure funding of RM6 million to go on to the clinical phase.

Finding a cure

In its attempts at finding a cure for oral cancer, the CRM team has been focusing on immunotherapy.

Currently in the preclinical stage, its immunotherapy project is expected to be ready for clinical trials, for testing on humans in 2019 – after the vaccine has been approved by regulatory bodies such as the Malaysian National Pharmaceutical Control Bureau and the United States’ Food and Drug Administration (FDA).

“As the name (immunotherapy) suggests, it’s basically (about) finding ways of activating the immune system of the patient in order to fight the cancer,” explained Cheong.

Her team has successfully discovered several antigens or proteins that are unique to oral cancer. These discoveries, which have been patented, led to further research that showed oral cancer cells are dependent on these antigens to grow.

“This means if we can put a ‘red flag’ on these antigens, our immune system can be activated and trained to recognise cancer cells as the enemy and eliminate them,” she said.

She explained that in most cancer cases, for reasons still not clear, the immune system’s army of white blood cells would somehow become “dazed” by the cancer cells, thus rendering them incapable of identifying the cancerous cells as threats.

“So basically what we do is take bits of the tumour and make molecules that look like the tumour cells.

“We then use these cells to activate white blood cells and get them back to work, just like vaccinations,” Cheong said, adding that the therapeutic vaccine has proven to work in the laboratory.

Why oral cancer?

According to Cheong, CRM – an independent, non-profit cancer research organisation – was focusing its research on oral cancer mainly because the disease was a significant burden in Asia.

“Because it’s very much an Asian disease, most of the pharmaceutical companies that are Western-based do not invest in it.

“This is why we really need to do it, because if we don’t, then nobody is going to.”

Oral cancer is a type of head and neck cancer and the sixth most common cancer in the world. It is highly associated with the practice of tobacco smoking, betel quid chewing and excessive alcohol consumption.

More recently, however, for reasons that are still unclear, oral cancer is increasingly being diagnosed in individuals who do not practice those risk habits.

Although the disease can be detected fairly easily, its death rates are higher than many other cancer types due to the fact that it is often presented late.

Oral cancer accounts for 11% of cancer deaths in Southeast Asia, compared to only 4% of cancer deaths globally.

In Malaysia itself, statistics show that two persons are diagnosed with oral cancer every day. Unfortunately, due to the lack of awareness, 75% of them seek treatment at the late stage.

Cheong said in Malaysia, about 50% of the patients survived less than two years, which meant that half of the oral cancer patients surviving today would no longer be alive two years down the road.

Symptoms of oral cancer include ulcers that do not heal for a long time, white patches inside the mouth that do not vanish when rubbed, and loose teeth.

Preventive vaccine

CRM’s Head and Neck Cancer Research team, comprising computer scientists, technologists, biologists and statisticians – who are all Malaysians – has come a long way over the last 10 years. Not only is the vaccine cure for oral cancer well within its grasp, the team is also in the process of coming up with another vaccine that can prevent the development of oral cancer.

Cheong said 80% of oral cancer cases were preceded by pre-cancerous lesions, like ulcers and white patches, inside the mouth that were easily visible.

“If we can develop a vaccine to prevent these lesions from becoming cancerous, it can potentially benefit a large number of patients and save a lot of costs for treatment,” she said.

As for the preventive vaccine project, CRM is collaborating with the United Kingdom’s Southampton Experimental Cancer Medicine Centre (ECMC). They have received a RM3.3 million grant from the UK-based Global Challenges Research Fund.

In a media release issued last December, Gareth Thomas, a professor of experimental pathology at ECMC, said although oral cancer was a bigger problem in Asia, it was also a significant and growing problem in the UK. Hence, steps to tackle its global incidence would have an important global impact.

“A cost-effective vaccine strategy that can target pre-malignancy before the cancer develops will transform the management of this disease worldwide,” he said.

CRM’s ground-breaking oral cancer research efforts are laudable and a huge achievement for Malaysia’s scientific community.

As Cheong puts it, “We were able to achieve this (UK grant and recognition) based on our work on the cancer in Malaysia… (oral cancer is something) people will not work on (but we did) and it is a huge achievement for Malaysian scientists.”

Coming up next, smartphone app to detect oral cancer

To further strengthen their efforts in fighting cancer, specifically oral cancer, CRM is also working on developing a smartphone application called Oncogrid.

With this app, dentists and community health personnel can take pictures of the mouths of patients suspected of having oral cancer and send them to clinical experts for evaluation.

Currently, there are only three known applications with similar capabilities in the world: two in the United States and one in India.

“Dentists and other individuals involved in primary healthcare can be given additional training to identify precancerous oral lesions,” Cheong said, adding that Oncogrid would help them to consult oral medicine specialists who would be able to recommend the appropriate course of action.

This was especially important when screening for oral cancer in rural areas where access to specialists, or public transport to the hospital, was scarce, she added.

CRM, meanwhile, has successfully completed a feasibility study on Oncogrid in Limbang, Sarawak, with the collaboration of Universiti Malaya and the health ministry. The results of this study showed that the app possessed enormous potential to be used widely.

Cheong said CRM was now in the process of developing the beta version of the app, with the final product expected to be ready by the third quarter of this year.