A small biotech company in India is producing a cutting-edge cancer treatment known as Chimeric Antigen Receptor (CAR) T-cell immunotherapy, locally dubbed NexCAR19. CAR-T therapy, pioneered in the United States, is primarily used to treat blood cancers and has seen significant growth in recent years. The cost of the Indian CAR-T therapy is one-tenth that of similar commercial products globally.
In scanning electron microscope images, T cells (pink) are seen attacking cancer cells (yellow). Image source: Steve Gschmeissner/SPL.
According to Nature, the NexCAR19 therapy from ImmunoACT, based in Mumbai, costs between $30,000 and $40,000 for a single treatment. The first CAR-T therapy was approved in the US in 2017, with current commercial CAR-T therapy costs ranging from $370,000 to $530,000, excluding hospital-related expenses and the cost of treating side effects.
The Indian drug regulatory authority approved NexCAR19 for use in India for treatment last October. In December of last year, ImmunoACT began offering treatment to paying patients, currently treating over 20 individuals each month across various hospitals in India.
"It's a dream come true," said Alka Dwivedi, an immunologist working at the National Cancer Institute (NCI) in the US who helped develop NexCAR19. For these patients, all other treatment options have failed, she noted. "And now, they are gradually being cured."
"This is very positive news. Hope is the word that comes to mind," remarked Renato Cunha, a hematologist at a cancer treatment institution in São Paulo, Brazil, indicating that Indian products could pave the way for advanced cell therapies in other middle- and low-income countries.
Terry Fry, an immunologist and pediatric oncologist at the University of Colorado, said that the product also serves as a test for researchers in high-income countries. "Even in places like the US, exposing researchers to the cost of making CAR-T cells would motivate them to act quickly."
NexCAR19 is similar to its counterparts in the US but differs in crucial aspects. Like four of the six CAR-T therapies approved by the US Food and Drug Administration (FDA), it targets CD19—a marker found on B-cell cancers. However, in existing commercial therapies, the antibody fragment at the end of the CAR is typically from a mouse, limiting its persistence as the immune system identifies it as foreign and eventually clears it. Therefore, in NexCAR19, Dwivedi and colleagues added human proteins to the mouse antibody fragment.
Laboratory studies suggest that this "humanized" CAR exhibits anti-tumor activity comparable to mouse-derived CARs and induces lower levels of cytokine proteins. This is crucial, as some cancer patients undergoing CAR-T therapy experience an extreme inflammatory reaction called cytokine release syndrome, which can be life-threatening.
Early clinical trials of NexCAR19 in adults with various forms of lymphoma and leukemia indicate that out of 33 treated individuals, tumors completely disappeared in 19 after one month of follow-up. An additional 4 individuals saw their tumors shrink by half, resulting in an overall response rate of 70%. Participants will be followed up for at least 5 years.
Natasha Kekre, a hematologist at the Ottawa Hospital in Canada, noted that these results are based on a small number of participants with a range of blood cancers, making it difficult to assess the efficacy of this treatment for specific cancers.
Only two participants experienced more severe cytokine release syndrome, and no one had neurotoxicity—another common but transient side effect of CAR-T therapy.
Rahul Purwar, founder of ImmunoACT, suggested that "humanizing" the CAR may be one reason for the therapy's safety. However, some argue that this link has yet to be established.
While the cost of this therapy remains high for many Indians—whose annual per capita gross national income is less than $2,500—NexCAR19 brings hope that the production costs of CAR-T therapy could be lower in other countries and regions. To reduce costs, the team entirely developed, tested, and manufactured the product in India, where labor is cheaper than in high-income countries.
To introduce the CAR into T cells, researchers typically use expensive lentiviruses. Steven Highfill, an immunologist at the National Institutes of Health Clinical Center in the US, said that in the US, purchasing enough lentiviral vectors for a trial with 50 people could cost up to $800,000. However, scientists at ImmunoACT manufactured these gene delivery vectors themselves.
Highfill stated that Indian researchers have also found a cheaper method to produce these engineered cells on a large scale, saving the costs of expensive automated machines.
Purwar mentioned that compared to some of the FDA-approved products, the therapy's safety has been further improved, further lowering patient costs—most patients do not need to spend time in intensive care units.
Purwar hopes to further reduce costs and expand production scale. ImmunoACT plans to export this therapy to Mexico and develop new products, including drugs for treating a disease called multiple myeloma.
