InVitroJobs: How long will it take until patients can receive tailored virotherapeutic anti-tumour drugs?

Prof. Dr. Ulrich Lauer: We can’t tell yet, because not that many patients have been treated with virotherapeutics yet. That also has to do with the fact that we don’t yet know when or how much of the virus we can or should administer. During a study on skin cancer, the patients received subcutaneous virus injections every fourteen days. In our studies in Tübingen the patients are given a virus infusion into the abdominal cavity every four weeks.

InVitroJobs: Are there any side effects? After all, conventional treatment such as chemotherapy or radiotherapy can have severe side effects.

Prof. Dr. Ulrich Lauer: So far comparable side effects mostly haven’t been observed.
However, the patients do notice that they have viruses in their bodies. They develop higher body temperatures around 38 °C, as is the case with normal infections. They also get headaches and body aches, which usually disappear after two days. These typical side effects mean that the immune system is responding to the virotherapeutic, which is in fact positive, as the immune system is definitely responsible for part of the anti-tumour effect and is trained by the viral stimulus to fight tumour cells it previously missed.

InVitroJobs: Is the effect of the virotherapy on primary hepatic tumours better detectable than the effect on metastases?

Prof. Dr. Ulrich Lauer: It is true that that is known methodological problem. Since the liver is one of the organs with an especially high autofluorescence, the marker gene signals expressed by the virotherapeutic – in this case GFP – are hard to make out. Metastases which do not come from liver cells have no such autofluorescence, which means that our marker proteins are very good to detect. The reason for that is in the liver itself, as the liver’s function as the main organ for metabolism, biosynthesis, catabolism and detoxification means many proteins are produced which are stimulated in the same fluorescence wave length (so-called fluorophores).

InVitroJobs: Is it true that ß-galactosidase and chemokinase play a part in the virotherapy technology?

Prof. Dr. Ulrich Lauer: That’s right. You can either use wild type viruses or recombinant altered viruses, which can for instance be encoded for marker genes (such as GFP, ß-galactosidase) or immunostimulant genes (such as GM-CSF). This gives us many possibilities for using viruses as an expression platform.

InVitroJobs: What is the situation regarding patients who are to be treated with virotherapeutics based on measles vaccines but have not yet contracted measles or been inoculated.

Prof. Dr. Ulrich Lauer: All measles virotherapeutics are produced on the basis of measles vaccines. This means that the patients basically get an additional measles immunisation in the course of their virotherapeutic tumour treatment. It is a very interesting question why measles vaccination viruses selectively kill tumour cells. What we are dealing with here is a general mechanism. Unlike normal body cells, tumour cells generally have no intact defence program against viruses, a consequence of the many mutations which take place during the mutation process. This makes tumour cells particularly vulnerable for viruses in comparison to body cells. This is the Achilles heel of tumour cells with respect to virotherapy.

InVitroJobs: Is it possible that the virotherapeutic might mutate?

Prof. Dr. Ulrich Lauer: In principle it is possible, but that hasn’t been observed so far. We use vaccination viruses which have proven stable over decades. In our own laboratory tests we were able to show that after at least 5 cell passages the virus remained 100 per cent identical to the original virus. The question is: how many mutations have to occur in a virotherapeutic before it mutates back to being a harmful virus (with wild type properties). Based on the current state of knowledge this would require very many mutations, making the probability of such a mutation extremely small.

InVitroJobs: Why did you use immortalised kidney cells (so-called vero cells) from the African Green Monkey in your research work?

Prof. Dr. Ulrich Lauer: Vero cells were established as far back as 1962 and are available via the cell bank ATCC. Vero cells have a special property which makes them especially interesting for virus research: they have a defect that makes it impossible for them to produce the transmitter interferon. Therefore vero cells cannot fight off virus infections and are particularly suitable for virus production.

InVitroJobs: Animal experiments are artificial. Why can’t scientists make greater use of patient tissue obtained from surgical operations?

Prof. Dr. Ulrich Lauer: Animal experiments are basically artificial and human-specific material does deliver more meaningful results. We know that animal experiments deliver good standardised results but cannot reproduce the variability of the tumour biology of our cancer patients. For this reason we currently still test our therapy method both on animals and in human operation material.

However, our medium-term objective is to replace at least a part of previous animal experiments using our new methodology (testing virotherapeutics on human operation material).
Nonetheless, we must first evaluate the equivalence of both methods exactly, so that the approval bodies for clinical experiments (in the case of virotherapy, the Paul Ehrlich Institute) can forgo specific animal experiments in the future and accept our new, more patient-specific methodology as a replacement. In order to achieve this, we need additional research funding and are currently submitting a corresponding application to the Federal Ministry of Education and Research.

Thank you for the interview.


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