Kees Melief wins Science and Society Prize

Prof. Dr Kees Melief

Immunohaematologist Pof. Dr. Kees Melief won the Science and Society Prize on 6 November for his research into a vaccine for cervical cancer.

'The concept of this vaccine is the result of 15 years of work with preclinical animal models and subsequently in clinical trials,' Melief said on accepting the prize. 'Initially there was a general sense of disbelief from the funds providing the subsidies whether this concept could work, but ultimately the clinical research was funded by the Nederlandse Kanker Bestrijding (Dutch Cancer Society ) (Koningin Wilhelmina Fonds).'

The prize was presented in the Ridderzaal on the Evening of Science and Society which is organised annually by a wide ranging forum of prominent Dutch individuals and companies. Melief was elected from eight finalists, after having been nominated by Leiden University earlier in the year.

Cervical cancer which for women is the second cause of death from cancer worldwide, is one of the few cancer types caused by a virus, the human papilloma virus (HPV). There are many different types of HPV, two of which (HPV16 and HPV18) are responsible for 70 to 75% of all cases of cervical cancer. 

Immune system

Human papilloma virus

The immune system should react against a virus. In the case of cervical cancer, this reaction is inadequate. Melief and his colleagues Van de Burg, Kenter and Offringa, have studied the possible causes for the immune system often being unable to prevent an HPV infection from leading to cervical cancer. Equipped with that knowledge they have developed a vaccine. 

Vaccine destroys infected cells
Vaccines that had been developed previously have only a preventive function and their effect is based on virus-neutralising antibodies, which eradicate the virus in the bodily fluids and mucous membranes before it has infected the cells. The vaccine developed by Melief and his colleagues, on the other hand, is based on cellular immunity: it causes the immune cells (T-cells) to receive the signal to destroy an infected cell. A weakness in the immune system is the fact that the (dendritic) cells that should set that process in motion are themselves insufficiently activated.

Licence to kill
The immune system works in a series of phases. The T-cells that migrate from the lymph glands to the area of the disorder, destroy the infected cells. But it is not as easy as that.

First the other cells, the dendritic cells, bring aberrant protein particles to the T-cells, and order them to destroy the abnormal cells: the licence to kill signal. But these dendritic cells, in their turn, must be activated by the T-helper cells. And this is where things go wrong, because the T-helper cells do not always take action. The vaccine developed by Melief and his colleagues activates these T-helper cells effectively during a lengthy period of time. It consists of the characteristic protein particles of the two cancer-inducing proteins of the HPV virus. These protein particles are absorbed and processed by the dendritic cells, that first activate the T-helper cells, and then present their protein particles and transfer their licence to kill signal to the 'killer' cells.

HPV infection: to the left, healthy cervical tissue; in the middle, the phase in which the virus multiplies, and to the right, the integration of the virus into the DNA of the cells. This is where the virus DNA sets a process of malignant change in motion. The vaccine is directed against these DNA-affected cells.

Powerful and longlasting response
Prototypes of this vaccine appear to have been active in mice and rabbits that had been infected with a papilloma virus. Under the management of Prof. Gemma Kenter in the Department of Gynaecology in the LUMC (Leiden University Medical Center), the first clinical experiments were conducted with patients who had a pre-malignant disorder caused by the high risk human papilloma virus type 16 (HPV16). These experiments demonstrate that in a substantial number of patients (4 out of 11) the abnormalities caused by the virus disappeared, while the virus itself was no longer evident in 3 of the 4 patients. Both in the animal models and in the patients, this was accompanied by a powerful and longlasting immune response. In 2005, Melief founded ISA (Immune System Activation), to produce the vaccine.

Kees Melief
Prof. Dr. Kees (C.J.M.) Melief (63) is professor and member of staff of the Department of Immunohaematolgy and Blood Transfusion of the LUMC. He was head of department from 1991 until 2005. He is a prominent, internationally renowned researcher with more than 400 publications to his name, some of which have been published in reputable magazines such as Nature and Cell. He belongs to the select group of highly cited scientists, acknowledged by the well-known institute Thomson Scientific (ISI) in Philadelphia. He is a member of the Royal Netherlands Academy of Arts and Sciences (KNAW).

Melief is also coordinator of the Clinical Applications Platform of the national Genomics Initiative, the 'Centre for Medical Systems Biology'. Here, research is being done to determine whether cervical cancer patients present a special genetic variation, whereby specific examination is made of the infected cells and components of the immune system.

The CMSB offers an ideal environment to conduct this complex research. Melief is also a stimulating university teacher, at different levels. More than fifty researchers have completed their PhD's under his supervision. Finally, mention should also be made of the fact that Melief has already received a number of prizes for his work, including the Akzo Nobel prize in 1995.

The distribution of cervical cancer in annual numbers of new patients per 100,000 women. The disease occurs mainly in areas where an early diagnosis and treatment are not readily available.

Valuable social effect
The prize consists of a specially designed sculpture and 25,000 euro intended for expenses directly concerned with this research.

The eight finalists presented their research at the Evening of Science and Society. To be nominated as a finalist, academic research of a high quality is considered that is exceptionally innovative and which offers the prospective of valuable social significance. At least one academic publication on the subject of the research in question (an article or monograph) of a recognised high stature must have appeared in a publication, or otherwise a patent must have been issued, between the period of 1 June of the previous year and 1 June of the current year.

Link
Evening of Science and Society (in Dutch)

(7 November 2006/HP)