17th International Meeting of the European Society of Gynaecological Oncology (ESGO 2011) 11—14 September 2011, Milan, Italy

Immunotherapy developments in cervical cancer

Professor Hans Nijman – University Medical Center, Groningen, Netherlands

Within gynaecological cancer you’re going to think of all kinds of modalities to try and do the best for patients. A lot of effort is done on surgery - how to improve it, chemotherapy, targeted therapies. My idea, based on the things I have done in the past, is that immunotherapy is the thing to go for, that’s what it’s all going to be about in the near future. It’s not a fact that it is already an established tool which a lot of patients are going to benefit from but it’s there and it’s coming. One of the main simple things which you can tell at this moment is that we have, for cervical cancer, a prophylactic vaccine, something which fifteen years ago people would have felt as being impossible and it’s there now, millions and millions of young girls being vaccinated with a prophylactic vaccine preventing the disease. So within ten or fifteen years I have no doubt that we will have therapeutic vaccines as well, being an important part of treatment for patients with cancer.

Can you explain the HPV vaccine and are there any other vaccines in development for other cancers?

It’s a prophylactic vaccine; prophylaxis means you have to be there before you are confronted with what you need to get your prophylaxis for. You are going to get confronted with this virus the moment you have sexual intercourse so you have to do it before the age of fifteen, sixteen. So therefore the ideal age for the prophylactic vaccine is ten to twelve years of age, that’s for prophylaxis. Looking at HPV, prophylactic vaccines are there but therapeutic vaccines are in a clinic already at this moment; not FDA or EMEA approved but they are there and they are also clinically effective. Looking at other types of cancer – ovarian, endometrial, it’s a question of time and looking at all the drugs being available and have shown their great potential within diseases like melanoma and kidney carcinoma, known types of cancer where the immune system has an important role, it’s a question of time that those modalities who are working there are going to be used within gynae cancers as well, not as a modality treatment in itself but to be combined with traditional treatment arms, being chemo, being radiotherapy. It’s important to know, which not many physicians who are treating patients with gynae cancer are familiar with, is that the traditional things like radiotherapy and chemotherapy are not that effective if the immune system isn’t doing what it is doing. That’s only the basis for having other treatments to be combined with the traditional ones to get the immune system getting the job to be done better than it’s already doing at this moment.

What are the current vaccines being researched in the gynaecological field?

The ones most easy to understand are those which are monoclonal antibodies, monoclonal antibodies to specific parts within the immune system in which they stimulate the immune system to do their job better or preventing the immune system to step on the brake. In other words, to let the immune system go and go and go instead of what naturally is happening, that you put on the brake for the immune system otherwise it will destroy you as a human being. And those drugs are available, quite easy to make, available ready on the market, and that’s the next step where we will be heading for. Next to other modalities which are harder to understand and harder to implement because they are more patient tailored. It’s harder to make, like within prostate cancer which is now an FDA approved drug, which is a dendritic cell-based vaccine made especially for every patient. It will be a question of time but that will be happening in other types of cancer as well, for instance in ovary. Get out your T-cells from that patient, educate them where they have to go for and then give it back to the patient. The future is ours.

If there are already prophylactic vaccines, why are therapeutic ones being developed?

That’s a very vital question to ask. It tells you all about the fine tuning of the immune system. The immune system, the T- and the B-cells, look at the T-cells for instance. They are educated in life when you are very young up to you’re at the age of one or two years of age. The T-cells are educated what’s normal and not to touch that, that’s what we call looking at what is self, what is not to be harmed. Everything which is not self, so non-self, is danger; if you get infected with an influenza virus, your immune system recognises that as being non-self, there is a danger and it needs to cope with it. So the essential thing is, in the end, how does that immune system know that a cancer cell is different from a normal cell, which flags are waving on that tumour cell telling ‘Hey, I’m a tumour cell, kill me’? Those are there but it’s a fine-tuned mechanism where we need to understand more about, but those flags are there on tumour cells. And in the end with the immune system and fine-tuning it, it’s still more delicate, more easy to understand that that is what we have to go for compared with chemotherapy. Chemotherapeutics don’t know what’s a normal or a tumour cell, they just kill every dividing cell, within the immune system, the fine-tuning we need to work on it but the flags are there on the tumour cell and we will make use of it.

How do the therapies differentiate between the normal cell and the cancer cells?

Answering the question is more or less simple in a way, the prophylactic vaccines are now on the market for the age of twelve to fifteen. So that means that all the girls and women, being older, are not getting that prophylactic vaccine. So for that age group and all those being older we still need to develop new treatment approaches, being also therapeutic vaccines. Asking the same question in fifty years from now, then yes, the answer should be that there is not a real market anymore. Although be aware that the prophylactic vaccine is against HPV16 and 18, so there are still eight other oncogenic HPV types which are not within the prophylactic vaccine and which we have to deal with.