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MC Explains | CAR-T cell therapy and why it raises hopes of better treatment for cancer

CAR-T cell therapy is approved only for blood cancers and lymphoma as of now, but research is on to understand its usefulness for solid tumours and even auto-immune diseases

June 30, 2022 / 11:22 AM IST

Two biotech startups in India are conducting clinical trials to establish the efficacy and safety of their versions of Chimeric Antigen Receptor-T cell (CAR-T) therapy before the cutting-edge immunotherapy is commercially available for cancer patients.

The trials are being conducted by ImmunoACT, incubated at the Indian Institute of Technology, Bombay, which has entered into a partnership with Hyderabad-based pharmaceutical company Laurus Labs, and Immuneel Therapeutics, which is based in Bengaluru and is backed by Biocon founder Kiran Mazumdar-Shaw and US oncologist Siddhartha Mukherjee.

Both companies plan to make the therapy available in India at a fraction of the cost overseas. How is the therapy better than conventional cancer treatments and how does it work? Moneycontrol explains:

What is CAR-T cell therapy?

Chimeric Antigen Receptor (CAR)-T cells are a patient’s own immune cells that are genetically engineered in the laboratory to fight cancer.

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Experts say a specific type of white blood cells called T cells are changed in the lab so they can find and destroy cancer cells. It is also sometimes referred to as a type of cell-based gene therapy because it involves altering genes inside T cells to help them attack cancerous cells.

Rahul Purwar, associate professor at IIT Bombay and founder and CEO of ImmunoACT, told Moneycontrol that as part of the therapy, T cells are taken from a patient’s blood and are changed in the lab by adding a gene for a receptor (called a chimeric antigen receptor or CAR), which helps the T cells attach to a specific cancer cell antigen.

The CAR-T cells are then transferred back to the patient through a procedure similar to blood transfusion. Once inside, these cells work like a “living drug” against cancer cells. The patient who has received this therapy needs to be under close medical supervision for weeks.

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Since different cancers have different antigens, each CAR is made for a specific cancer’s antigen. In types of leukaemia or lymphoma, the cancer cells have an antigen called CD19.

The CAR T-cell therapies to treat leukaemia or lymphoma are made to attach to the CD19 antigen and would not work for a cancer that does not have the CD19 antigen.

In what types of cancer can it be used?

Research has shown that the therapy is mostly effective in blood cancer and lymphoma (cancer beginning in the cells of the lymph system). In India, about 40,000-50,000 patients of these cancers are diagnosed every year.

CAR-T cell is a prospective therapy that has ushered in a new era of curing refractory and stubborn cancers, said Dr Rahul Bhargava, principal director, haematology department at Fortis Memorial Research Institute, adding that investigations are on to assess the therapy’s efficacy for ovarian and oesophageal cancers as well.

“We have understood, after much investigation and scientific research, that T cells are the ones that help in actually killing the bad cells,” he said.

Are there conditions for its use?

Presently, the therapy is offered as a second or third-line treatment for late-stage leukaemia and lymphoma patients who are either not responding to conventional treatments like chemotherapy and bone-marrow transplants or have a case of relapsed cancer.

Dr Sivasubramaniam, a senior medical oncologist with Prashanth Hospitals in Chennai, said that CAR-T cell therapy is normally used as the third line of treatment while chemotherapy is the first choice.

“If a patient recurs, we usually go for bone marrow transplant but since we don’t have many options for third-line treatment, this concept has emerged,” he said.

Research from abroad has shown that the therapy can be effective in 40-50 percent of the patients, with slightly better results in paediatric populations.

However, experts said that CAR-T cell therapy can be offered as a first-line therapy in the future, going by its effectiveness in a large number of patients.

“Even people who were given CAR-T cells in 2010 are still alive, showing that the majority of cancers which are refractory to chemotherapy and bone marrow transplant can still be cured by virtue of CAR-T cells,” said Bhargava.

What are the possible side-effects?

Immunity can be a double-edged sword. So sometimes, the therapy induces Cytokine Release Syndrome (when chemicals called cytokines are released into the blood it can send body’s immunity into an overdrive) that can even be life-threatening and needs immediate medical attention.

According to Sivasubramaniam, another problem that may arise is neurological toxicity, which may affect the central or peripheral nervous systems, though these are rare side-effects.

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However, because of these possibilities, CAR-T cell therapy cannot be practiced in all hospitals.

“That’s because it needs training in handling the drug as well as managing complications,” Sivasubramaniam said.

Indian companies working to develop the therapy in India, meanwhile, say that their drugs are far more safe than those available in the US and Europe.

How can patients access the therapy?

Till some time ago, cancer patients willing to get treated using this therapy had to go to developed countries like the US. However, the two companies in India that are conducting clinical trials for their therapies are looking to launch it in the country by late 2023 or early 2024.

As of now, clinical trials for the therapy are under way at Tata Memorial Centre in Mumbai and Narayana Hrudayalaya in Bengaluru.

How much does CAR-T cell therapy cost?

The therapy costs about Rs 3-4 crore in the US. The Indian biotech-startups carrying out R&D locally say they will make it available at a fraction of this cost.

ImmunoACT has estimated that its therapy may cost about Rs 25 lakh per patient when it becomes commercially available. Immuneel said its therapy is likely to be available at one-fifth to one-seventh of the cost in the US.

 
Sumi Sukanya Dutta
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