We hope Indian ingenuity will help make cellular therapy for cancer affordable, says Dr Siddhartha Mukherjee

Cancer physician, scientist and author of Pulitzer-winning, The Emperor of All Maladies, Dr. Mukerjee,, is setting up a cellular therapy facility in Bengaluru in the hope of developing drugs. On the sidelines of an event, he tells why personalised medicine and diet are the next frontier for cancer treatment.

At your lab in Columbia University , you and your team of scientists are researching ' living rugs' made from our own cells for cancer treatment. How does this cellular therapy work and what is its potential?
In some forms of leukemia, we could not achieve good results because drugs couldn't distinguish between cancerous and healthy cells. When we attacked the cancer cell, we also attacked the normal one. The idea we patented in my lab is to use gene editing to change the normal cells. For much of the history of cancer, we've focused on cancer cells. Here, we're inverting the logic and saying let's make the normal cells resistant to the therapy with help of gene editing, thereby making the cancer uniquely sensitive to therapy. This uses the human body, the host of cancer, as the element of change. We couldn't change the normal cells earlier because we didn't have the tools, Gene editing provides us with those tools. And all of a sudden, cancer becomes exposed.

How did you think of approaching the problems like this?
The idea occured to me while I was onvacation to Mexico city. I was making drawing with my daughter. One way to make a drawing is to make a black silhouette on white paper. And you can also make a white silhouette in black paper. And I was doing these drawings and began to realise that in cancer we've been using the cancer silhouette against the normal host as the paradign for all treatments. But what if we used the  host as the background and then attack cancer cells? We patented the idea and showed that it can eradicate this untreatable form of leukemia--- acute myeloid leukemia--- in animals and we're rapidly progressing to human studies.

What more can cells tell us about cancer?
A 2nd approach to cancer, we've taken is to ask the question whether other kinds of cells in the body, apart from T-cells, can be used for immunotherapy. One particular type of cell which has never been harnessed before is myeloid, which is a white blood cell and our body's first line of defence against infection. These can penetrate solid tumours, such as ovarian cancer and breast cancer, where Y-cells have not been very successful. A final and 3rd area that we've worked on extensively is personalising cancer medicine. The great irony of cancer is that while it grows so rapidly inside the body, it is difficult to cultivate outside in a lab. But work done by Dutch molecular geneticist, Hans Clevers in the past 10 years whose how to grow cancer cells in a dish. The cells multiply to make a 3-dimensional cluster called an organoid. So, now we take an individual's cancer cells, grow then in a dish and find out what cancer it is and what drugs does it respond to. This allows us to individuate cancer therapy. We're just about to publish a paper to show how you can find completely new cancer drugs and therapies. We're slowly moving away from the protocol-driven therapies which are sort of one-size-fits-all.

The food-is-medicine approach is a grey area in modern science. But your lab is researching the impact of diet on cancers. What have you found so far?
 
We. as a community, have neglected diet for long. Diet is part of the micro-environment of cancer cells, which sustains them. We- and many more labs- have started studying the role of diet in a highly systematic and scientific manner. Certain chemotherapies lead to a rise in blood sugar and hence insulin, which controls sugar. It's a side-effect. And insulin allows cancer cells to become resistant to a particular form of chemotherapy. By reducing the amount of insulin, for instance, through manipulation of the diet ( consuming lots of protein, little fat and no carbs) you can make cancers sensitive to chemotherapy. It's important to note that it's a combination of diet and drugs. The diet on its own won\t help. Human trials for this study are about to start. We\re testing it for lymphoma and endometrial cancers.

You've set up a cellular therapy facility in Bengaluru. Why did you choose India?
 
This is a collaboration with Kiran Majumdar Shaw. We hopefully will be able to deliver T-cell therapy and other cell therapies which have previously been unavailable in India. While the facility has already started we're not producing cells yet because you require incredible infrastructure to make these living drugs. Why India? Because we hope it will bring down the cost of these therapies. In India, the combination of engineering and scientific ingenuity has been able to bring the costs down in IT and tech industries. We are hoping to use the same innovative capacity of local scientists and doctors to be able to reduce the cost five to ten fold and make cellular therapies accessible to more people.


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