Indian Scientists Develop CAR-T Therapy, with U.S Inspiration

Indian Scientists Develop CAR-T Therapy, with U.S Inspiration

Cancer is becoming a concerning public health issue in India, with new cases reaching nearly 1.6 million in 2023 and with 800,000 people estimated to die from cancer each year. Many new cancer treatments are inaccessible in India due to high costs and lack of insurance coverage. Additionally, some treatments such as CAR T-cell therapy require hospitalization to manage severe side effects, which is challenging given limited hospital access for many Indians.

Dr. Rashmi Dwivedi and colleagues at the Indian Institute of Technology Bombay and Tata Memorial Center aimed to develop an affordable, humanized CAR T-cell therapy with reduced side effects compared to approved therapies that use mouse antibody fragments. After struggling to design an effective CAR T -cell, they visited the National Cancer Institute (NCI) at Bethesda, Maryland in 2017 through a training program.

At NCI, they worked with Dr. Nirali Shah, Terry Fry, and others to learn CAR -T cell design, manufacturing, and clinical trial development. With NCI’s guidance. they successfully manufactured several humanized CAR T -cell versions targeting CD19, a protein on leukemia and lymphoma cells.

Actalycabtagene autoleucel, like most of the CAR T-cell therapies approved in the United States, targets CD19, a protein that is often produced in large amounts on the surface of leukemia and lymphoma cells.  One version, actalycabtagene autoleucel (later named NexCAR19), showed potent anti-cancer effects with limited immune reactions in preclinical studies.

Credit: National Cancer Institute

In 2021, the first clinical trial began treating 14 acute lymphoblastic leukemia patients with NexCAR19, followed by a 64-patient trial in leukemia and lymphoma. Results showed 68% of lymphoma and 72% of leukemia patients responded, with no neurological side effects and only 5% experiencing severe cytokine release syndrome. In contrast to $400,000 for approved CAR T therapies in the U.S., NexCAR19 is expected to cost around $50,000.

Dr. Shah highlighted that the Indian team not only developed an effective, affordable CAR T therapy, but built an entire cellular therapy infrastructure that other low-to-middle income countries can model. This global collaboration demonstrates how scientific teamwork can overcome barriers to accessing cutting-edge cancer treatments worldwide.


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