EUREKA project E! 3172 NKSTIM has produced a new potential drug to stimulate cancer patients' own 'natural killer' cells to attack and eliminate cancer cells; currently undergoing clinical testing in patients with leukaemia or myeloma. Existing knowledge of how transplanted bone marrow cells eradicate tumours gave the foundation for designing the new drug.
Providing the remaining clinical trials are successful, the drug will offer the first real treatment option for older people with acute myeloid leukaemia, whose age precludes them from bone marrow transplantation. It also promises improved options for treating other types of cancer, such as multiple myeloma and lymphoma.
Myeloid leukaemia is characterised by rapid growth of abnormal white blood cells in the bone marrow, and it may exist in acute (AML) or chronic (CML) forms. AML is more prevalent among older people, where it is virtually incurable; progressing rapidly and only 10% of patients survive more than 5 years. The best treatment for leukaemia is bone marrow transplantation, which provides fresh donor-derived immune cells. One type of these - the 'natural killer' (NK) cells - release cytotoxic substances that can destroy abnormal, cancerous white blood cells without affecting the normal blood cells. The effectiveness of NK cells in various types of cancer has been reported in both mice and humans. The problem is that bone marrow transplantation is not available to elderly patients, because their general health status rarely supports the very arduous transplantation procedures.
To avoid the need for bone marrow transplantation, the NKSTIM project set out to design and generate a drug that would stimulate the patients' own NK cells. The project brought together the biotechnology skills of the French SME, Innate Pharma, with Novo Nordisk, a large biopharmaceutical manufacturer from Denmark. The project defined the type of molecule needed, used a rational and highly targeted approach to generate it, and developed the methodology to validate it.
Stimulating the patient's own immune response
At the start of the project in 2003, Innate Pharma had already identified a new generation of protein molecules able to stimulate NK cells through their specific receptors, unaffected by the activity of cancerous or infected cells which would normally suppress an immune response. On this basis, Innate Pharma and Novo Nordisk set out to discover candidate therapeutic molecules suitable for administration to humans.
A few suitable proteins were selected and taken through initial drug characterisation. The most promising candidate was identified and Novo Nordisk then supported the regulatory evaluation, pre-clinical and Phase I clinical trials for safety and dose testing. By the end of the EUREKA sponsorship (at the end of 2006), the Danish company had produced the drug in a form that could be administered to patients for safety and efficacy evaluation in Phase I and II trials. Innate Pharma is now continuing the trials toward market authorisation; anticipated to be within 6 years.
Fast and promising development
The identification of the new potential drug was very fast. "We did not need to look at many alternative candidates," says Nicolai Wagtmann, Vice President at Novo Nordisk, who led the project through the discovery phase. "This was not a traditional massive drug screen, but quite the opposite. We started from an understanding of the disease and the biological mechanism effective in transplantation, the precise molecule in the body that we wanted to modify, and a clear idea of how that had to be done."