In Germany alone, more than 15,000 people are diagnosed with renal cell carcinoma every year. This figure seems to be high, but the tumour, which arises from malignant epithelial cells in the kidneys, is nevertheless one of the less frequent cancers. This is the reason why the pharmaceutical industry has not invested heavily in the search for suitable therapies for renal cell carcinomas. The market for a drug for the treatment of this disease is rather small, and the majority of companies are afraid of not being able to cover the high costs required for the development of such a drug.

But new therapies for the treatment of kidney cell carcinoma are urgently needed. At present, the prospect of cure is only given in the early stage of disease, when the tumour has not yet spread to other organs. However, about fifty per cent of patients are diagnosed very late, at a stage when the cancer has spread and it is no longer possible to remove the kidney alone. Classical chemotherapy and radiotherapy are ineffective. New, recently approved chemotherapeutics have improved the treatment of the disease, but the tumour still cannot be cured. Now, a new cancer vaccine produced by immatics biotechnologies GmbH might finally bring about the breakthrough that has long been hoped for.

“It has been known for a long time that renal cell carcinomas react to drugs that stimulate the body’s own immune system,” said Dr. med Jürgen Frisch, CMO of immatics. For example, some patients can be treated with interleukin-2 (IL-2) or interferon (IFN), which are able to keep the tumour in check, at least for some time. However, this therapy has serious side effects and reduces the patients’ quality of life considerably. “The treatment with IL-2 only leads to an unspecific immune response, which reduces the prospect of recovery,” said Frisch adding “we have developed a strategy that enables us to attack the cancer cells directly. In addition, the substance is well tolerated by the patients.”

The immatics scientists base their developments on the fact that renal cancer cells have characteristic structures on their surfaces. These structures are known as TUMAPs, tumour-associated peptides, which do not occur in healthy tissue. These TUMAPs act like antigens, similar to bacteria or viruses, and are recognised by the immune system and subsequently eliminated. In order to support the body’s immune defence against the tumour, immatics developed a vaccine (IMA901) which contains ten such TUMAPs. “This leads to a highly specific immune response, and we expect that this response will be able to destroy the tumour cells selectively,” said Frisch, explaining the new concept.

immatics uses a patented analysis and production method to identify and synthesise the TUMAPs. “Our approach is unique,” said Frisch explaining that the approach clearly differs from the approaches of the company’s competitors. Some companies use vaccines that are produced for each individual patient from the patient's own tumour material. Frisch is sure that this method is not only less effective, but also more prone to mistakes and far more expensive. “You have to obtain tumour material from each individual patient in order to produce vaccines. This is very time-consuming and has huge requirements on quality control because the production process is always an individual process.” He is also sure that this approach does not always make sure which antigens are included in the individual vaccines.

IMA901 is produced in standardised processes and is suitable for almost all patients suffering from renal cell carcinoma. “We were able to show that about 90 per cent of the patients had one or more of these TUMAPs on their tumour,” said Frisch. The more the better – because the tumour cells try to fight off the attack of the immune system by downregulating certain surface antigens. “But because we are using several TUMAPs at the same time, the probability is quite high that we can circumvent the strategies adopted by the carcinoma,” said Frisch.

Now it remains to prove the efficacy of the cancer vaccine in practice, which seems so plausible in theory. In a clinical phase-1 study, immatics showed that the IMA901-induced immune response correlates with the stabilisation of the disease. “In addition, the patients tolerated the drug extremely well,” said Frisch.

The drug has been tested in a Europe-wide clinical phase-2 study since September 2007, the results of which will be available at the end of 2009. immatics will also test whether the combination of the vaccine with other substances – for example with standard chemotherapy – increases the efficacy of treatment. “We have to be open for all aspects,” said Frisch, “after all, active immunotherapy for the treatment of cancer is completely new.”

If the trials result in a positive outcome, then immatics hopes to launch IMA901 in about five years’ time. The drug has received orphan drug status from the European EMEA and immatics hopes that this status will eventually pay off the high development costs. Orphan drug status not only facilitates the approval procedure, but also prolongs the patent of the drug. “By giving a drug orphan status, governments can motivate companies to invest in the development of therapies for rare diseases,” said Frisch.

However, immatics has found another way to refinance the research costs. “We assume that the method involving synthetic TUMAPs is, in principal, suitable for the treatment of numerous tumours, not only for the treatment of renal cell carcinoma,” said Frisch. The company has started to analyse and test about half a dozen of different tumours in the laboratory. The initial results are encouraging. A colon cancer vaccine has already entered clinical testing, a glioblastoma vaccine is about to enter clinical testing. This is a good reason for Frisch to be optimistic about the future: “Active immunotherapy is a great opportunity in the treatment of cancer, and our approach is as good as, if not better than many other approaches that are on the market.”

sb – 27 August 2008 © BIOPRO Baden-Württemberg GmbH

Further information:
immatics biotechnologies GmbH
Dr. med. Jürgen Frisch
Paul-Ehrlich-Straße 15
72076 Tübingen
Tel.: +49 (0)7071 565125-0
Fax: +49 (0)7071 565125-99
E-mail: frisch@immatics.com