In a significant breakthrough for global cancer care, India has successfully developed and commercialized its first indigenous chimeric antigen receptor (CAR) T-cell therapy, offering a life-saving treatment option at just one-tenth the cost of similar therapies available internationally.
The therapy, named NexCAR19 (actalycabtagene autoleucel), was developed by researchers at the Indian Institute of Technology (IIT) Bombay in collaboration with Tata Memorial Hospital, Mumbai. It received approval from India's Central Drugs Standard Control Organisation (CDSCO) in October 2023, marking a milestone in the country's biomedical research capabilities.
A More Affordable Cancer Treatment Option
While CAR T-cell therapies in the United States typically cost around $400,000 per treatment, NexCAR19 is priced at approximately Rs 40 lakh ($50,000), making it possibly the least expensive CAR T-cell therapy globally. This dramatic cost reduction makes cutting-edge immunotherapy accessible to a much broader patient population in India and potentially other low- and middle-income countries.
"This is a big achievement for India," said Dr. Alka Dwivedi, one of the key researchers behind the therapy who began exploring the possibility of developing an India-specific CAR T-cell therapy in 2015 while a graduate student at IIT Bombay. "It's the team effort that brought us here."
Dr. Rahul Purwar, founder and CEO of ImmunoACT, the spin-off company from IIT Bombay that funded the clinical trials and will manufacture the therapy, described the development as "a dream come true and an incredible win for the patients in India and countries with limited resources."
Promising Clinical Results
The approval of NexCAR19 was based on two small clinical trials conducted in India involving 64 patients with advanced lymphoma or leukemia. Results presented at the American Society of Hematology meeting in December 2023 showed that 67% of evaluable patients (36 out of 53) experienced a significant decrease in cancer, with approximately half achieving complete remission.
Among the 53 patients who could be evaluated (38 with lymphoma and 15 with leukemia), 26 lymphoma patients (68%) and 10 leukemia patients (72%) responded to the treatment. Notably, all responses in the leukemia group were complete responses, meaning patients showed no signs of cancer following treatment.
Innovative Design Reduces Side Effects
A key innovation in NexCAR19 is its "humanized" design. Unlike the six CAR T-cell therapies approved in the United States, which contain antibody fragments derived from mice that can trigger severe immune reactions, the Indian therapy uses a more human-like antibody structure.
This design modification appears to have significantly reduced side effects. None of the 53 participants in the clinical trials experienced the neurologic side effects commonly seen with U.S.-approved CAR T-cell therapies. Only 5% developed severe cytokine release syndrome, an immune-related complication, and just five patients required hospitalization due to side effects.
Dr. Saroj Prasad Panda, head of pediatric oncology and hematology at SUM Hospital, Bhubaneswar, explained: "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."
How CAR T-Cell Therapy Works
CAR T-cell therapy represents a revolutionary approach to cancer treatment that harnesses the body's own immune system. The process begins by collecting T-cells from the patient's blood. These cells are then genetically modified in a laboratory to produce chimeric antigen receptors on their surface, which enable them to recognize and bind to specific proteins on cancer cells.
The modified T-cells are multiplied in the laboratory before being infused back into the patient's bloodstream. Once reintroduced, these engineered cells can identify and destroy cancer cells throughout the body.
"The CAR T-cells are made from the T-cells of the patient after reprogramming them in a laboratory setting," Dr. Panda explained. "The cells are then grown and multiplied in the lab before infusion in the patient's body. It then recognizes and binds to specific proteins on the surface of cancer cells directly killing them."
International Collaboration and Knowledge Transfer
The development of NexCAR19 was facilitated by international collaboration, particularly with the U.S. National Cancer Institute (NCI). In 2017, Dr. Dwivedi and her colleagues traveled to the NCI's Center for Cancer Research through a visiting scientist program sponsored by NCI's Center for Global Health.
There, they worked with leading experts in CAR T-cell therapy, including Dr. Nirali Shah, who studies these therapies for children with blood cancers. The team learned the entire process, from designing effective CAR T-cells to manufacturing them at clinical grade and conducting proper clinical trials.
"It is remarkable that they were able to generate a brand new CAR T-cell therapy that matched the results being seen in the United States," Dr. Shah said. "The fact that they have been able to keep the costs low and come up with a treatment that is relatively well tolerated means that they're going to improve the lives of so many people."
Addressing India's Growing Cancer Burden
The development comes at a critical time for India, where cancer is becoming an increasingly significant public health challenge. New cancer diagnoses in the country reached nearly 1.6 million in 2023, up from about 980,000 in 2010. Approximately 800,000 people die from cancer annually in India, a number expected to grow substantially in coming decades.
Despite this growing burden, many new cancer treatments remain inaccessible to most Indians due to high costs and limited insurance coverage. NexCAR19 represents a significant step toward addressing this gap.
Current Applications and Future Potential
Currently, NexCAR19 is approved for patients aged 15 and above suffering from B-cell cancers, including B-cell acute lymphoblastic leukemia and various forms of lymphoma. The therapy is expected to be available for pediatric patients soon, with trials currently underway at Tata Memorial Centre.
ImmunoACT is building a manufacturing facility in Mumbai with plans to develop additional sites across India. Initially, they aim to treat approximately 1,200 patients annually. The therapy is now available in over 30 hospitals across about a dozen cities in India.
Dr. Nataraj KS, senior consultant in Haemato Oncology at HCG Cancer Centre, Bangalore, noted that clinical trials are also ongoing to evaluate CAR T-cell therapy's potential role in treating solid tumors, including glioblastoma, cervical cancer, head and neck cancer, and lung cancers.
Multiple academic institutions and healthcare providers, including CMC Vellore, HCG Hospitals, and Apollo Hospitals, are now working to develop additional affordable and accessible CAR T-cell therapies. This increased competition is expected to further improve accessibility and reduce costs.
Challenges and Limitations
Despite its promise, CAR T-cell therapy does have limitations. Dr. Nataraj pointed out that while the therapy has shown remission in patients with certain blood cancers, longer follow-up has revealed that durable remissions may be lacking in some cases.
The therapy also requires specialized facilities and expertise to administer safely. "The therapy should be administered only in specialized hospitals with experience as it may cause severe, life-threatening toxicities," Dr. Nataraj cautioned.
Additionally, the preparation of altered T-cells currently occurs only in specific facilities, which need to be expanded to meet the growing demand from patients across the country.
Nevertheless, with a success rate reported at over 80% in preventing relapses during initial trial phases, NexCAR19 represents a significant advancement in cancer treatment in India and a model for how developing countries can create innovative, affordable solutions to address their unique healthcare challenges.
