BHUBANESWAR: India has emerged as a leading healthcare player in cancer care with its own innovative immunotherapy, which costs just one-tenth of the traditional treatments offered abroad.
The indigenously developed chimeric antigen receptor (CAR) T-cell therapy that genetically reengineers a patient’s immune system is now a new frontier treatment for blood cancers.
One of the newest, and very promising treatments, the therapy uses the body’s own immune system against cancer. Developed by IIT Bombay in collaboration with Tata Memorial Hospital, Mumbai, the therapy was approved last year for commercial use by the Central Drugs Standard Control Organisation (CDSCO).
Unlike traditional cancer treatments, the therapy is tailored to each patient’s unique genetic makeup and specific characteristics of their cancer. The home-grown NexCAR 19 (actalycabtagene autoleucel) is now available in over 30 hospitals in around a dozen cities in the country.
Patients aged above 15, who are suffering from B-cell cancers, are eligible for this treatment. It is expected to be available for paediatric patients soon after the trial, currently underway at Tata Memorial Centre.
Although six CAR T-cell therapies have been approved by the Food and Drug Administration (FDA) in the US for clinical use, they all contain antibody fragments derived from mice, which may sometimes trigger side effects. The Made in India therapy, however, involves modification of T-cells to carry a more human-like antibody. This humanised CAR T-cell therapy has been successful in escaping immune system attack.
Dr Saroj Prasad Panda, head of paediatric oncology and haematology at SUM Hospital, Bhubaneswar, said unlike chemotherapy and radiation, which kill both healthy and cancerous cells, this immunotherapy targets only cancer cells with better precision.
“CAR T-cells are like administering patients a living drug. The CAR T-cells are made from the T-cells of the patient after reprogramming them in a laboratory setting to produce proteins on their surface for a receptor called chimeric antigen receptor. The cells are then grown and multiplied in the lab before infusion in the patient’s body. It then recognises and binds to specific proteins on the surface of cancer cells directly killing them,” he said.
So far, the foundations of cancer treatment have been surgery, chemotherapy and radiation therapy. Even as new categories of treatment have helped transform the treatment landscape for people with cancer and emergence of targeted therapies, they are either not long term or there are reports of relapses after a limited period.
However, with a success rate of over 80%, the CAR T-cell therapy has been successful in preventing relapses in its initial phases of trials. As cancer cases in the country are projected to rise in the coming years, which can go beyond 15 lakh per year from next year and the death of around 10 lakh patients, the therapy is set to revolutionise cancer treatment.
Dr Neeraj Siddharthan, head of clinical haematology at Amrita Hospital, Kochi, said CAR T-cell therapy offers new hope for previously untreatable conditions. “CAR T-cell therapy represents a ground breaking approach to cancer treatment, with the potential to provide long-term remission and care for certain types of blood cancers. The therapy, which is very expensive (around `4 crore to `5 crore abroad), is now being made affordable in our country with some indigenous developments,” he said.
Different types of cancer have different antigens. Each kind of CAR T-cell therapy is made to fight a specific kind of cancer antigen. So the therapy made for one type of cancer won’t work against another type of cancer. Clinical trials are also ongoing for its role in solid tumours like glioblastoma, cervical cancer, head and neck cancer and lung cancers.
Multiple industries and academic institutions like CMC Vellore, HCG Hospitals and Apollo Hospitals are now working to get more affordable and accessible CAR T-cell therapies. Since more partners are involved in developing the therapies, the country will have more accessibility and scalability leading to reduction in the cost of therapy.
Dr Nataraj KS, senior consultant, Haemato Oncology and Transplant Physician at HCG Cancer Centre, Bangalore, said the CAR T-cell therapies approved to treat blood cancers in the US are primarily against B-Cell lymphomas and some forms of acute lymphoblastic leukemia and chronic lymphocytic leukemias and, most recently, in multiple myeloma.
“India has taken significant strides in the field of CAR-T cell therapy. The first home-grown CAR-T cell therapy called NexCAR19 has shown promising results. Another indigenous CAR-T cell therapy with varnimcabtagene autoleucel (IMN-003A) industry sponsored trial demonstrated excellent safety and efficacy outcomes with deep and durable responses including absence of severe neurotoxicity. It is expected to be available for commercial use soon,” he said.
CAR-T cell therapy, however, has some limitations that researchers and clinicians are actively addressing. It has shown remission in patients with B-cell precursor acute lymphoblastic leukemia and B-cell lymphomas, but longer follow-up has revealed that durable remissions are lacking.
“As T-cells multiply to destroy cancerous cells, they can release large amounts of chemicals called cytokines into the blood, which can ramp up the immune system. The therapy should be administered only in specialised hospitals with experience as it may cause severe, life-threatening toxicities. Besides, preparation of altered T-cells that occurs only in some specific facilities currently needs to be expanded to cater to large demand from patients,” Dr Nataraj added.
What is CAR T-cell Therapy?
Chimeric antigen receptor (CAR) T-cell therapy is a cancer immunotherapy treatment that uses immune cells (T-cells) genetically reengineered in a laboratory to enable them in locating and destroying cancer cells more effectively.
Which cancers can this treat?
Currently, CAR T cell therapy is approved to treat several types of haematological malignancies, including leukemia (B cell acute lymphoblastic leukemia), multiple myeloma and lymphoma. Common subtypes of lymphoma where this treatment is effective include diffuse large B-cell lymphoma, follicular lymphoma, high-grade B-cell lymphoma, mantle cell lymphoma and primary mediastinal large B-cell lymphoma.
Who can seek this therapy?
Eligible candidates for CAR T-cell therapy are those patients who do not respond to standard therapy or have relapsed after at least two-three other treatment regimens.
How does it work?
CAR T-cells are genetically altered to have a new receptor on the surface for specific cancer cells. When a CAR T-cell comes in contact with an antigen on a cancer cell, it activates. The activated CAR T-cells multiply and signal to other parts of the immune system to come to the site of the cancer cell. These signalling proteins are called cytokines. All of these cytokines and activated T-cells then cause significant inflammation focused at the cancer cell and kill the cancer cells.
What are the side effects?
Most common side effect of CAR T-cell therapy is cytokine release syndrome (CRS). The symptoms include fever, chills, low blood pressure, confusion and difficulty in breathing. Another potential side effect is neurologic symptoms such as confusion, trouble in speaking and tremors or seizures. Though the effects are short term and generally reversible, it may require a stay in an intensive care unit. Long-term effects of CAR T-cell therapy are yet to be known.
What is the approximate cost of the therapy in India?
NexCAR19 (ImmunoACT) costs approximately Rs 40 lakh. It is possibly the least expensive CAR T-cell therapy in the world.
(With inputs from Anna Jose @ Kochi and Aknisree Karthik @ Bengaluru)