Dr Siddhartha Mukherjee: ‘Using customised diet as a drug is the fifth pillar in anti-cancer therapy’ | Idea Exchange News,The Indian Express
Dr Siddhartha Mukherjee is an eminent oncologist and Pulitzer award-winning author. He’s rolling out a significant clinical trial on treatment of cancer, called the Chimeric Antigen Receptor (CAR) T-cell therapy, which has already been used in several countries.
Oncologist Dr Siddhartha Mukherjee on the crisis in the health economic system in India, attempting to cure blood cancer through sophisticated cell therapy, deploying strategies to prolong remissions and keeping costs down
Kaunain Sheriff: Can you take us through the breakthrough therapy that you are introducing in India and the science behind it?
Let’s begin with immunotherapy against cancer. It comes in many variations but there are three main ones. First are monoclonal antibodies (MABs) which have been in use for a long time. The second is T-cell therapy. This does not involve transfer of T-cells but uses your own native cells. In order to prevent your own T-cells from attacking themselves, you inactivate them so that you don’t get autoimmunity. Some examples of autoimmunity would be Type 1 diabetes, lupus and arthritis. So, your body basically keeps a check on these T-cells and inhibits them. These drugs are called checkpoint inhibitors, some of which are available in India. Obviously, if you activate your T-cells against cancer, they can also be activated against your normal cells. So, checkpoint inhibitors are necessary. The third variant is the CAR T-cell therapy, where we extract T-cells from a cancer patient’s body and we use a virus, which is a modified and inactivated version of the HIV virus but doesn’t cause HIV, to deliver genes into them. These genes then weaponise the T-cells to attack cancerous cells. In other words, we remove the T-cells from the body through apheresis, they go into an extremely sterile laboratory, are activated with gene therapy and harvested in incubators until they expand to a very large number and are frozen. This process usually takes about 10 to 14 days before the cultured cells are transfused back into patients.
Originally, when this was done in the US by several people, including Michel Sadelain at Memorial Sloan Kettering and very successfully by the UPenn group, led by Carl June and Bruce Levine, there was scepticism about whether these highly activated T-cells would attack the tumour which had spread considerably. The results were quite remarkable and almost miraculous. These patients were on the verge of death and mostly had liquid cancers or leukaemia as their tumours had stopped responding to multiple cycles of chemotherapy. We also tried to ensure that the activated T-cells, that would release cytokines or chemicals that T-cells use to communicate with each other and with the immune system, wouldn’t generate a cytokine storm. We controlled it with medicines. Since then, we’ve already dosed several patients. A group in IIT is also dosing patients using the same formula. Theirs is a phase one trial, ours is a phase two trial. Theirs is a new product, ours is a clinically exposed product that has already been proven to be successful in humans. We have in-licensed it from Barcelona, it has already completed trials in Spain and has been proven to be both safe and extremely effective. We are giving the doses of T-cells in not one shot but in three or four shots, depending on how we do at the trial.
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