• Professor John Gribben of The London Clinic

Health

Q&A: Prof John Gribben

Consultant medical oncologist at The London Clinic on blood cancers, stem cell transplants and research into the immune system

Interview: Viel Richardson
Image: Joseph Fox

What is haematology?
Haematology is the study of blood disorders. Within that there are different sub-specialties and I specialise in cancers of the blood. My own particular interest is investigating how we get people’s immune systems to fight cancer.

At what point did haematology specifically begin interesting you?
I was always very interested in science as well as medicine and with haematology, there is both a laboratory-based, scientific component and a ward-based component where you look after patients.

Why is the relationship between haematology and other sciences so close?
Haematology lends itself very well to research because it is very easy to get samples of blood from a patient. The whole field of oncology has been led by what haematologists have been able to do, because of how easy it is for us to get hold of leukaemia and lymphoma samples to study. Actually, a lot of the early work to discover what causes cancer and what changes occur in cancer cells was done in the field of haematology.

Has it been effective?
Absolutely. Both successful and exciting. One of the most exciting things about this field right now is that there is a whole new set of targeted medicines being developed as a result of this approach—drugs that work in a very different way to the old chemotherapy drugs.

Can you explain the difference?
Cancer cells divide more rapidly than others. With old chemotherapy drugs, we killed all dividing cells. But the science showed us that there is a very specific DNA change that takes place within the cancer cell, which led us to investigate and then develop a drug that switches off the gene driving that change. It has been very effective.

Can you give us an example of a successful new treatment?
There is a type of leukaemia that I look after called chronic lymphocytic leukaemia. These are cancers of B-cells, which are driven by something called the B-cell receptor. There are B-cell receptor antagonists that have just been approved this year which have revolutionised the way we treat this disease.

Another example is in acute lymphoblastic leukaemia where we use what we call a bi-specific antibody. It has two arms: one latches on to the cancer cell and the other latches on to an immune cell. The antibody then brings them together, so the immune cell can destroy the cancer cell.

This has revolutionised the treatment of these cancers, and it is particularly effective for people who have very high risk factors. These people would have died a couple of years ago—now we are able to offer them treatment that involves taking a tablet every day. No hair loss, no nausea, no vomiting. This class of patient has gone from having pretty much no hope to having very successful treatment available to them.

Prof John Gribben

What areas are you struggling in?
It is more of a general frustration really. There are some types of leukaemia where the treatments we are giving now are not too dissimilar to the ones we were giving 20 years ago and we have not been able to develop safer, more effective treatments. What is frustrating is that there is a lot of science to tell us why the patients are not responding well to chemotherapy, but we do not have the drugs as yet to move them forward. But we can identify when a patient will not be cured by chemotherapy, so we can tell them right from the start that it’s just one stage of the process while we try to find them a bone marrow donor.

Does technology play a large part in your field?
Yes it does. There is technology in our stem cell laboratory that we use to manipulate bone marrow cells once we have collected them. Then there is technology that allows us to create things like the bi-specific antibody I mentioned earlier.

Have technological advances had much impact on bone marrow transplant methods?
The old-fashioned method of doing a bone marrow transplant was to collect physical bone marrow from donors. What we are after during a transplant are stem cells found in the bone marrow. We have developed a machine that can collect stem cells from the donor’s blood, so there is no need for the physical operation. The great thing is the stem cells we get from these machines are actually better.

What do you do with the stem cells?
We use them to regenerate the patient’s immune system, which will have been severely damaged or destroyed by chemotherapy. We take the donor’s stem cells and create the type of cells we need for that patient, then introduce them to the patient’s system. The new immune system from the donor is able to recognise the leukaemia cells that are left in the body and attack them. We call that a ‘graft versus leukaemia’ effect.

Does this mean the end of bone marrow donations?
Not yet. For very complex reasons paediatricians sometimes still prefer the old style, and there are still some other circumstances where the physical bone marrow is a little bit better. But nine out of 10 transplants are done using stem cells taken from the blood, so we now refer to it as a stem cell rather than bone marrow transplant.

What other impact has this had?
Once we understood the graft versus leukaemia effect, the obvious question was, do we still need to kill so many cancer cells with high doses of chemotherapy and radiotherapy? And the short answer was no. So now we do mini transplants where we give very low doses of chemotherapy, which is designed to suppress the patient’s immune system, then we add the donor stem cells.

I believe this ties with your area of research?
Very much so. My area of special research is the investigation of the patient’s immune system, and why it cannot do what the donor immune system does. Cancer cells have developed very effective ways of disrupting the patient’s immune system. They can do this because it is controlled by brakes as well as accelerators. The cancer cells exploit those brakes by producing something called checkpoint inhibitors, which switch parts of the immune system off.

We were one of the laboratories that discovered this activity, and we now have what we call a checkpoint inhibitor antibody, so we are no longer targeting the cancer cells, but the mechanism that it uses to stop the immune system. We can start using the patient’s own immune system to target the cancer. It’s incredibly exciting.

What do you like about what you do?
I really enjoy the research stage, but I am also passionate about my connection with the patients. I often see them over a long period of time, so I get to know them and their families. There is a real sense of satisfaction when I see a treatment that I have prescribed working.

The flip side of that is we get to know patients who we cannot cure and unfortunately succumb to the cancer, and this can hit you very hard. But it is what provides me with the motivation to get back into the lab to work harder and try to find a treatment, so that the next time I see a patient in their circumstance, we can provide them with a happier outcome.