After 13 years of investigation, a multidisciplinary team, made up of researchers from the universities of Buenos Aires and Quilmes, the Roffo Institute, the Garrahan hospital, the Academy of Medicine and the Argentinian company Elea, is in the forefront of the latest innovations in cancer research. In the next few months it will initiate an international study which will test the effects of a vaccine developed in the country to treat lung tumours.

It consists of a Phase III clinical trial, the final stage that is required by health authorities before permission can be requested for the approval of a pharmaceutical product. 760 patients from Argentina, Brazil, Cuba, India, Malaysia and Singapore will be involved, with the possibility that later on European patients will be included.

The details of this project illustrate how it is possible for a private company and the public sector to work together in research. The Elea laboratory took on the know how of Argentinian researchers and contributed to a substantial part of the project’s finance. These investigators carried out all aspects of the project, from the design of the medicine to it’s clinical application. The study is included in the Programme of Strategic Areas of the ‘Agencia Nacional de Promoción Científica y Tecnológica’ (The National Agency for Scientific and Technological Development).

'For a Latin American country, this is something special. A great discovery', emphasises Doctor Daniel Alonso, director of the ‘Laboratorio de Oncología Molecular’ (Laboratory of Molecular Oncology) of the University of Quilmes and researcher in Conicet.

The group is working on a number of lines of research which aim to attack the residual illnesses of cancer. Amongst these the most developed is the so called ‘therapeutic’ vaccine. Whilst it stimulates the immune system, it does not prevent the disease, but is designed to complement conventional treatment techniques.

As is normally the case, the idea of designing a vaccine which can stimulate the immune response against the actual tumour cells arose from a conversation. “It is well known that in every type of cancer there is an immunological reaction, but that it is inefficient", says doctor Hugo Sigman , director of Elea. ‘During a visit to two partner centres in La Habana, one of Molecular Immunology and the other of Genetic Engineering, we wondered what we could do to make the immune system attack the tumour effectively. And from that conversation emerged the molecular target, an antigene that in some cases is found in cancerous cells. Looking back now, it was a utopian project'.

Immunological privilege

The journey which has taken us to where we are now was a step by step process, not exempt from the obstacles which are common to all ambitious research.

'In the first publication, we showed that the compound was not toxic', explains Doctor Leonardo Fainboim, chief researcher of Conicet and director of the Immunogenetic Centre of the Clinicas Hospital. “We then carried out a Phase II in breast cancer and announced for the first time that the vaccine releases an anti-tumour cell response. That enabled us to move forward'.

As the researcher explains, it is very difficult to attack the tumour because it is transformed in a place which is immunologically privileged. 'In this sense, I think that one of the important things is that we are able to modify the local immune response in order to break that privilege', he adds.

The product chosen for this trial on a large scale is a monoclonal antibody (a product of the fusion of a mouse’s B lymphocite with a human tumour cell, which allows identical antibodies to be obtained, as they are produced by just one type of cell of the immune system) which behaves like a vaccine: it stimulates the immune system against a specific molecular target (ganglioside), which is this case is present in lung cancer cells.

The results of preliminary clinical studies made in the country, during which several hundred patients were injected with 15 doses of this compound, whose specific scientific name is antidiotype 1E10, for a period of fifteen days, are, according to the researchers, encouraging.

“We have essays published on patients with a high chance of relapse after standard treatment, such as melanoma surgery, or surgery, chemotherapy and finally hormonotherapy of breast cancer", explains Doctor Gabriela Cinat, director of the area of melanoma and sarcoma of the Clinical Oncology Department of the Angel Roffo Institute. 'These patients undergo conventional treatment, after which we know that at some point the illness will continue to advance. Our intention is to prevent this evolution, which is an important achievement, considering the prognosis. In a study which the American Association of Clinical Oncology will publish soon, carried out with 40 melanoma patients, 20 with breast cancer and a similar number with an advanced melanoma, even though the test was planned for six months, the patients ended up receiving the vaccine for two years. Despite the fact that this group is not homogeneous, what we are able to say is that we have very encouraging results and a average survival rate much higher than expected. Now we need more controlled studies'.

A chronic illness

Without important side effects, the vaccine is aimed at a specific molecular target which is more abundant in metastasis than in the primary tumour, something which is very convenient taking into account that it will be used as a complement to conventional therapies.

'We are aiming to reduce the tumoural load before initiating immunological treatment", explains Cinat. “ It has to be made clear that this treatment is not infallible, but that we hope that it can help to improve the life expectancy of the patients. In the first trials we have had some patients who have not relapsed, despite all the indications that this was likely to happen. We do not consider them cured though, calling them long-term survivors'.

'One of the hopes we have about cancer is to be able to convert it into a chronic illness", concludes Sigman. “Think about high blood pressure: patients who suffer this illness cannot be cured, but it can be kept under control. I do not believe that any of the treatments which we are trying out can eliminate the illness. The person will continue to suffer it but our aim is that they live longer and have a better quality of life'.

By Nora Bär

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