Immunity to cancer – pursuing the dream

Listen to the podcast for this interview

Professor Sir Leszek Borysiewicz was knighted in 2001 for his contribution to vaccine research, including the development of the cervical cancer vaccine. He gave the Jephcott Lecture on vaccine-based approaches to cancer prevention at the recent UK Royal Society of Medicine ‘Toward the Prevention of Cancer’ meeting on the 24th April 2007.

MedWire Reporter Cher Thornhill asks Sir Leszek to explain how scientists are harnessing the body’s immune system to prevent and treat cancer, and describe the impact these methods could have on clinical practice.

Doctors are familiar with conventional vaccines, like the polio vaccine, tetanus, and BCG, but cancer vaccines are relatively new. Why has it taken so long for these to come about?

I think there are two main reasons for this. The first reason is that it’s taken quite a bit of time to realize that about a quarter of worldwide cancers are potentially attributable to infection, and that means that approaches that have been useful in infectious disease can be applied as a primary prevention of cancer. The second reason is that to develop the kind of immunity to foreignness on cancer cells has been very difficult. It is not an easy way to induce the right immune response.

Vaccines have virtually eradicated some diseases. Will they offer a cure for cancer?

Now the question is whether we can prevent the cancer before somebody actually has the cancer, and that certainly is what is being attempted with papillomaviruses. It’s trying to prevent the first infection occurring so that actually you do not have the necessary criteria for a cancer to develop at this site. If that were to happen, can you actually model a situation where the cancer might disappear altogether? The answer’s “Yes, you probably can, but it’s going to take a long time.”

What about curing patients who already have been diagnosed with cancer?

Curing cancer is a much more difficult thing to do with immune systems. I can give you one example where it appears to work and that is in the Epstein Barr virus-induced B-cell lymphomas, particularly in those that occur in immuno-compromised patients, where an artificial infusion of cytotoxic T cells targeting the Epstein Barr virus component can actually control these diseases. So there are paradigms that suggest that it is possible, but we’re still a long way from practicality, patient by patient.

If we look at the preventative vaccines, what proportion of cancer types could they potentially prevent?

Well, I think we would start off by saying that virtually all of the infectious cancers, the 25 percent that I referred to earlier on of all attributable cancers that are due to infection – I think they would have to be the primary targets. So the big candidates are papillomaviruses, undoubtedly the helicobacter and its relationship with stomach cancer, so that is certainly a proposition, and the hepatitis viruses, particularly B and C, are really all targets.

You’ve just mentioned the key targets for preventative vaccines. Two vaccines have already been licensed in the USA – the hepatitis B virus vaccine and the cervical cancer vaccine – both of which are preventative vaccines. How do these preventative vaccines work?

They work by inducing neutralizing antibodies which prevent the infection with this agent in the genital tract. The big question that still remains with these vaccines is how long-lived will that immunity be, particularly bearing in mind it’s a very specific site you are immunizing against. So they’re working in the way that conventional vaccines such as anti-polio vaccines or anti-tetanus vaccines would work. I think the hepatitis C is the next big one that we’d have to look at because that is responsible for a large part of hepatocellular cancer that is not attributed to hepatitis B. And I think that that would be the one that we would really need to see come along next.

Some people refer to therapeutic vaccines as the true cancer vaccines. How do they differ from preventative versions?

Well, therapeutic vaccines really try to attack the cancer cell itself. They are usually dependent on different immunological mechanisms and very often these are not antibody mediated and the reason they’re referred to as the true cancer vaccines is that only about a quarter of vaccines can actually be targeted against specific infectious agents, which is great that we can actually target those, but if you have a cancer, such as lung cancer, which is due to a different type of carcinogen then you have to attack the cancer cell, and that is a very difficult problem, and there’s still an enormous amount of work to be done before we can overcome this in any significant way.

The prostate cancer therapeutic vaccine – sipuleucel-T – is awaiting FDA approval. Will this be a turning point for therapeutic vaccines?

Well, I hope so, but I think that until we actually see its utility in practice, only then are we going to be able to assess. I think the difficulty with therapeutic vaccines is that they’re only going to help a fraction of patients, and at the moment it’s difficult to predict which fraction is going to be particularly helped. So, yes, I certainly hope it makes an impact and it may well point the way toward therapeutic vaccines in other cancers as well.

Are there any other therapeutic vaccines in development that you’re particularly excited about?

There are certain ones which are particularly interesting, ones which might be more generic – if we could develop something which could tackle more than one type of cancer. And one area which I still am absolutely intrigued about are the heat shock protein-derived vaccines, which may actually be able to take off particular cancer antigens from heat shock-related proteins and to use these in a way to try to induce immunity. There’s a lot of work going on in Connecticut and Yale and elsewhere to cover some of this work and there’s some very exciting work I think still to come from that field.

Does that encompass what are sometimes referred to as universal cancer vaccines?

That’s the Holy Grail. And will we ever get there? I’m not sure. I think the trouble is the mutations that occur, the somatic mutations occurring in cancer cells are such that there are always going to be specificities, which we would call private specificities – that’s to you and your cancer – that have enabled these to happen. So whether we end up having to individualize therapy in this field is really an open question. Yes, a universal vaccine would be much more useful because we could apply it across the board. Do I see that as likely? Probably not.

Do you think therapeutic vaccines will see the same success as the preventative anti-infection versions.

For the reasons I’ve said, I think they’re always going to have more limited success and I think that they’re far more likely to be part of the modalities of treatment that are open to our management of patients with cancer into the future. So I do believe that they’re going to have an impact alongside chemotherapy, radiotherapy, and surgery, which are all modalities of treatment, and I think it’s more likely to be an additive effect rather than a substitution for more conventional treatments already available.

When do you expect to see therapeutic vaccines come into the clinic?

Well, some I think could be seen there as soon as 5 or 6 years down the line. Already one or two are seeking approval in the wider FDA context. So I think we will start seeing a trickle coming into this area.

As vaccines are traditionally associated with eradicating disease, could this pose a problem for doctors when counseling patients with cancer?

Yes, and I think that maybe one of the things that we have to think very carefully about is whether the use of the word vaccine is going to be appropriate in the therapeutic setting. I mean should we be talking about an immunotherapeutic rather than a vaccine, because patients have a particular view as to what a vaccine does and how it works. Their perception may well be very different, and therefore in helping them understand what is actually being offered and how this might help their individual case is something that doctors are going to have to spend a lot of time addressing with patients when they’re considering these forms of treatment.