India’s First CAR-T Cell Therapy Authorized for Cancer Treatment

When Alka Dwivedi was a graduate student at the Indian Institute of Technology (IIT) Bombay in 2015, she started to question if it would be possible to create a CAR T-cell therapy there.  
Several CAR T-cell treatments, a kind of immunotherapy in which a person’s T cells are altered in a lab to attack cancer cells only, were being evaluated at the time in US clinical trials. Additionally, even though CAR T-cell therapies appeared to be potential treatments for blood malignancies such as lymphoma and leukemia, once approved for usage, they were likely to be highly expensive and have serious adverse effects. 

Both problems, she believed, meant that many people in low- and middle-income nations like India would not have access to these innovative treatments—at least not in the form in which they were being produced now. To satisfy the requirements of cancer patients in their nation, Dr. Dwivedi and her team set out to build an alternative CAR T-cell therapy. However, they were aware that they needed help.  

After receiving her Ph.D. in 2021, Dr. Dwivedi set out on a cooperative path that took her to the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland, along with colleagues Rahul Purwar, Ph.D., of IIT Bombay, and Gaurav Narula, M.D., of Tata Memorial Centre in Mumbai.  

This team worked under the tutelage of eminent CAR T-cell therapy specialists at the NCI’s Center for Cancer Research while they were at the NIH Clinical Center. According to Dr. Dwivedi, the training given by NCI scientists—such as Nirali Shah, M.D., who specializes in CAR T-cell therapy for pediatric blood cancers—proved to be beneficial. During their visit, Dr. Dwivedi and her co-investigators were able to construct actalycabtagene autoleucel (NexCAR19), an effective CAR-T cell therapy that could be produced in India, made affordable, and satisfy the demands of patients in the country’s healthcare system.  

The Central Drugs Standard Control Organization, India’s equivalent of the US Food and Drug Administration, authorized NexCAR19 as the country’s first CAR-T cell therapy in October 2023.  

The clearance was predicated on the outcomes of two minor clinical trials that were carried out in 64 individuals with advanced leukemia or lymphoma in India. Trial results were reported in December 2023 at the American Society of Hematology convention. Of the 53 patients in the two studies, 67% had a significant decrease in the extent of their disease (objective response), and around half of them had a complete response, meaning that the cancer had completely disappeared.  

The trial was supported by ImmunoACT, an IIT Bombay spin-off that will also be producing and commercializing actalycabtagene autoleucel.  

“This is a significant accomplishment for India,” Dr. Dwivedi, who is currently pursuing her education at the NCI’s Center for Cancer Research, remarked. “Our collective efforts have led us to this point.”  

As the founder and CEO of ImmunoACT and the graduate adviser to Dr. Dwivedi at IIT Bombay, Dr. Purwar remarked in a statement that “this is like a dream come true and an incredible win for the patients in [India]”. “Our patients will now have affordable access to this life-saving medication in India and other developing nations with limited resources.”  

Cancer is quickly growing from being a minor public health concern to a major one in India. The country saw around 1.6 million new cancer diagnoses in 2023, up from roughly 980,000 in 2010, according to the most recent estimates. Additionally, it is predicted that 800,000 people (about half the population of Idaho) die from cancer each year; this number is projected to rise significantly over the next several decades.

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Even though the number of cancer cases in India is rising, many innovative cancer treatments are not widely available due to their expensive cost and the country’s overall lack of insurance coverage. Furthermore, many treatments—like CAR T-cell therapy—may have serious adverse effects that need to be managed in a hospital. This raises the expense of treatment and necessitates access to a local hospital, which isn’t the case for a large portion of the populace.  

Six CAR T-cell treatments have been authorized in the US to treat blood malignancies, mainly lymphomas, certain types of leukemia, and, most recently, multiple myeloma. However, all these approved treatments contain mouse-derived antibody fragments, which might have serious side effects when the patient’s immune system tries to reject the alien material.  

Dr. Dwivedi and her colleagues attempted to convert CAR T cells to carry a more human-like antibody, using a methodology that is being investigated by research groups both domestically and internationally. They believed that the immune system onslaught would be thwarted by this “humanized” CAR T-cell therapy.  

Dr. Dwivedi remarked, “We felt we should come to NCI and get trained.”  
A patient at Mumbai’s Tata Memorial Hospital got the first injection of actalycabtagene autoleucel, the CAR T-cell treatment that would eventually be developed into NexCAR19, on June 4, 2021. There were just 14 patients in this initial round of the clinical research, and they were all B-cell acute lymphoblastic leukemia individuals who had either relapsed or had not responded to conventional therapy.  
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Data from the trials were given by ImmunoACT cofounder Atharva Karulkar, Ph.D., and clinical trial leader Hasmukh Jain, M.D., at the American Society of Hematology meeting. Of the 53 patients who were able to be assessed, 15 had leukemia and 38 had lymphoma, and 26 of the 38 lymphoma patients (68%) and 10 of the 15 leukemia patients (72%) responded to the treatment. The leukemia group’s responses were all complete, meaning they showed no indications of cancer.  

Just 5% of the 53 individuals experienced cytokine release syndrome, a severe immune-related adverse effect. None of the participants experienced the neurologic side effects that are frequently observed in patients treated with CAR T-cell therapy approved in the United States. 

News Reference  

https://www.cancer.gov/news-events/cancer-currents-blog/2024/nexcar19-car-t-cell-therapy-india-nci-collaboration#:~:text=In%20October%202023%2C%20India%27s%20counterpart,with%20advanced%20lymphoma%20or%20leukemia.