In India and the US, around 10 per cent of all cancers are linked to blood, like leukemia. But the hope of these being cured by CAR T (Chimeric Antigen Receptors Therapy) are extremely promising, says American scientist Carl June, one of the pioneers in the field.

Slowly but surely, CAR T is emerging as the frontline therapy. Novartis is offering it in the US for leukemia at $475,000 with some guarantees, too. Gilead is another company with a CAR T drug while Bristol-Myers Squibb’s Celgene has promising remedies in the pipeline.

There is a growing interest in the area, and about 600 trials are on to test the use of CAR T cells. The focus has expanded to treating solid tumours, such as those in the lung, pancreas, brain and colon. And investments of $30 billion in the US and $50 billion in China have reportedly been made on developing targeted cell therapies, says June.

But the science of making CAR T cells has to improve; it is a major limitation now. “We grew them in labs in the 1990s, trained people for it. Now it has to be an automated process to gain currency. India is well positioned to make this on a large scale,” says June, who was honoured with the Genome Valley Excellence Award at the recently concluded BioAsia 2020 in Hyderabad.

Disruptive technique

CAR T cells are like a ‘living drug’ in the body. All it requires is one injection to get into the patient’s body, similar to a small blood transfusion.

Once it is mass-produced and clinical trials are done, it has the potential to be disruptive in the pharmaceutical sector, says June, who is Richard W Vague Professor in Immunotherapy, Director of the Center for Cellular Immunotherapies at the Perelman School of Medicine, and Director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania.

Traditionally, the main treatment lines against cancer are chemotheraphy, radiation and surgery. In recent years, targeted methods, where drugs attack the identified cancer cells, as seen with imatinib (Gleevec) and trastuzumab (Herceptin), have gained ground.

The latest line of treatment that is growing and attracting interest is immunotherapy. Here, the emphasis is on using the patient’s immune system to counter the cancer or tumour spread. Adoptive cell therapy, or harnessing the patient’s own immune cells to fight the cancer within, is fast making strides.

In this class, the most promising one showing positive advances in clinical development is CAR T. In 2017, two CAR T cell therapies were approved by the US Food and Drug Administration — one for the treatment of children with acute lymphoblastic leukemia (ALL) and the other for adults with advanced lymphomas. Experts, however, caution that it is still early days, as studying its efficacy against solid tumours is a long way away.

Synthetic molecules

CAR T cells are the equivalent of “giving patients a living drug”, says Renier J Brentjens of the Memorial Sloan Kettering Cancer Center in New York, another leader in the field. T cells are the backbone of the therapy, which requires drawing blood from patients and separating out the T cells. Next, using a disarmed virus, the T cells are genetically engineered to produce receptors on their surface, called chimeric antigen receptors, or CARs.

These receptors are “synthetic molecules, they don’t exist naturally”, explains June, who led several clinical trials in patients with leukemia. These special receptors allow the T cells to recognise and attach to a specific protein, or antigen, on tumour cells.

The French company Cellectis, in fact, has launched a Phase I (early stage) trial of its off-the-shelf CD19-targeted CAR T cell product in the US for patients with advanced acute myeloid leukemia.

The company’s product — which is made using a gene-editing technology known as TALEN — has already been tested in Europe, including in two infants with ALL who had exhausted all other treatment options. In both cases, the treatment was effective.

In trials done by Novartis on patients with end-stage leukemia, the success rate has been 82 per cent. Now, trials are on to use the therapy at the beginning stage, says June.

Papal approval

A significant boost to the therapy has also come from the Vatican. Pope Francis is positive about the treatment, and the Church has shown support.

June cites the example of Nick Wilkins, one of the patients whom he met at the Vatican and was recommended for treatment in 2015. After the therapy, he is able to attend college regularly and even play basketball, claims June.