What does immunotherapy mean?
Immunotherapy refers to the use of the person’s immune system to fight cancer. This term is not new; it has been around for a very long time.
The use of immunotherapy has been successful in treating various cancers even before the latest discoveries. It consists of either stimulating the patient’s immune system to work harder or more effectively in treating cancer or supplementing the body’s immune system with man-made immune proteins.
Why doesn’t our immune system respond to the cancer cells?
Whenever a tissue bearing foreign genetic material is introduced into your body, your immune system will naturally identify the tissue as being alien and mobilise your defence mechanism to reject it.
Why are cancer cells not eradicated by our immune system? Do cancers grow because the immune system is weak? No, a cancer patient’s immune system is actually intact.
So why does the immune system not reject tumours? Many years ago, my colleagues and I carried out a simple experiment. We took foreign genetic material that didn’t belong to cancer patients and injected it into the tumours. We discovered that the immune system was able to identify the tumours as being foreign and in 60 per cent of patients, the tumours shrank.
What it suggests is that cancer cells somehow have a camouflage, making them seem as if they belonged to the body, so the immune system did not bother with them and let the cancer grow and spread.
When we introduced foreign material into the tumour cells, the immune system could recognise that these cells did not belong and went on to tackle them.
We demonstrated the concept of camouflage. If you remove the camouflage, the immune system actually works.
How is this different from chemotherapy and radiotherapy?
The new class of immunotherapy drugs is very different because we are no longer focusing on the cancer cells. We focus instead on how to remove the so-called camouflage of the cancer cells and allow the immune system to take care of things.
This mode of therapy has been found to be effective in the treatment of certain lung cancers, malignant lymphoma and melanoma.
One of the big advantages of immunotherapy is that it has very little side effects; and this is very important because it means that you can use it at late-stage cancer treatment when the patient is feeling tired and generally weak. You can still deploy it even then because there are no significant side effects and does not affect quality of life.
Are we still at an experimental stage with immunotherapy?
The use of immunotherapy and our understanding of how best to use it is at its infancy. We have not uncovered the full potential of immunotherapy. It is definitely not a magic bullet that can cure all cancers.
Oncologists are very excited over immunotherapy because we are seeing occasional but dramatic responses.
The question we ask ourselves is why it works in some patients but not in other patients. When we can find out the reason, then we will be able to select and treat only the patients who are likely to benefit from this therapy.
Will immunotherapy be used for all cancers? What’s the status now?
Presently, we are seeing dramatic responses in only some individuals with specific tumour types and not across the board for all cancer patients.
We don’t deploy immunotherapy first-line treatment. Targeted agents and chemotherapy are still the first line of treatment.
But there will come a point – be it due to the toxicity of therapy or when one runs out of viable options – patients may have to seriously consider immunotherapy.
Our only caution is that not many patients are responding to this novel therapy. However, we are still very excited with it because some of the patients that respond to this therapy have very dramatic responses.
It is certainly worth discussing with your doctor if immunotherapy is applicable to you and whether it’s the right time to consider trying it.
What are the proportions in terms of patients responding well?
The number of patients treated with immunotherapy is still small. The response rates vary according to the type of cancer.
In melanoma, we are seeing a significant proportion of patients benefitting from immunotherapy – 50 per cent or more.
In lung cancer, we are talking about 10 to 20 per cent. So that’s why it’s not time to pop the champagne. However, in some patients whose tumour cells express higher levels of this protein called PD-L1, they are more likely to have longer overall survival and higher response rates, as show in a clinical trial involving more than 1000 patients.¹
There is no doubt that immunotherapy has generated a great deal of excitement and optimism amongst cancer specialists and patients. However, there are many unanswered questions that need to be addressed: How do we best use it? How do we select patients who are more likely to respond favourably? Do we combine treatments? Is there a role for combining immunotherapy with chemotherapy or targeted agents?
What other benefits are there to immunotherapy?
With chemotherapy or targeted therapy, the drugs are used to kill the cancer cells. As long as there are viable cancer cells, the treatment has to go on and on. This may be different with immunotherapy.
Theoretically, if immunotherapy succeeds in awakening the immune system to the presence of the cancer cells (by removing their camouflage), it may potentially continue to do the job even after the treatment has stopped.
If we can awaken the immune system and not have to continue treatment, for some patients, this may be the magic bullet we have been looking for.
Find out more about cancer and how to fight it on ST's Fighting Cancer microsite.
¹ Reference: Herbst et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016; 387(10027): 1540-50.