Two doctors, victory against cancer: Behind India’s low-cost CAR T-cell therapy

It began with a simple Google search. In 2015, Dr Gaurav Narula, 58, a paediatric haematologist-oncologist at Tata Memorial Hospital, was hoping for a breakthrough in immunology research. He’d quit the Navy in 2012 to pursue oncology and was focused on chimeric antigen receptor (CAR) T-cell therapy, a personalised cancer treatment that used each patient’s blood, specifically its T-cells (types of immune cells), genetically modifies these cells in the lab to give them cancer-fighting powers, and then infuses those CAR-T cells back into the patient’s body.
It began with a simple Google search. In 2015, Dr Gaurav Narula, 58, a paediatric haematologist-oncologist at Tata Memorial Hospital, was hoping for a breakthrough in immunology research. He’d quit the Navy in 2012 to pursue oncology and was focused on chimeric antigen receptor (CAR) T-cell therapy, a personalised cancer treatment that used each patient’s blood, specifically its T-cells (types of immune cells), genetically modifies these cells in the lab to give them cancer-fighting powers, and then infuses those CAR-T cells back into the patient’s body.
Dr Narula found Rahul Purwar, 46, a faculty member at the Indian Institute of Technology-Bombay (IIT-B), online. “I stumbled upon Purwar’s CAR T-cell PowerPoint while preparing for my own research paper on the subject and wrote to him,” says Dr Narula. “When we met in his laboratory at the IIT-B campus, I told him I needed a car, and he needed a driver.”
Purwar, a Lucknow native, held a PhD in molecular medicine from Hannover Medical School, Germany, and a postdoctoral fellowship in immunology from Harvard Medical College. He had joined IIT-B in 2013, giving up his interest in expensive CAR T-cell therapy and concentrating on T-cell biology and skin disorders instead.
The email from Dr Narula re-ignited his passion. “Let’s make this science-fiction a reality,” the oncologist told him. Who could have refused?
CAR T-cell therapy can be used when the disease has stopped responding to chemotherapy, which is the accepted treatment for most cancers today. Not only is each CAR T-cell treatment specific to the patient, the modified cells are designed to locate and destroy cancer cells in the body.
There’s only one problem: The cost of the treatment runs into crores per patient.
“Keeping in mind ongoing research, trials and clinical evidence abroad, my idea was to have a CAR T-cell therapy that would cause long-term cancer remission,” says Dr Narula. “We would then not need a bone marrow transplant”, which would especially help young patients.
Purwar expected it would take him two years to design the CAR T-cell therapy. Dr Narula says it was ready within six months. “Meanwhile, I had written to Dr Terry Fry (who then headed the CAR T-cell programme at the National Cancer Institute in Bethesda, USA) and told him I have a partner with whom I can explore the research work in India,” says Dr Narula.
Dr Narula has been mulling over the project for years. “In 1999, I took annual leave from the Navy and worked at the Tata Memorial Hospital (TMH), Mumbai, for a month. Two years later, I came back on study leave and did a fellowship in paediatric haematology-oncology there,” he says.
When he resigned in 2012, he joined the same hospital, hoping to figure it all out. This was the year that six-year-old Emily Whitehead of New Jersey became the first paediatric patient to receive CAR T-cell therapy for leukaemia, at the Children’s Hospital of Philadelphia. “A close friend sent me a clipping, knowing my interest in immunology and immune-haematology.”
“Till 2015, TMH’s paediatric department aimed to provide basic chemotherapy to children who came here. We aimed to raise funds and treat all patients regardless of monetary status. By the time we could manage to think of CAR T-cell therapy in 2015, the world was moving far ahead. There were three or four centres in the US already looking at trials. Whatever news we heard was very, very good,” says Dr Narula.
Dr Narula said Dr Fry and his team played a vital role, as they were the knowledge partners. “We visited NCI where they were working on this. Whenever we got stuck, he (Dr Fry) and his team guided us,” he says with gratitude.
Four years after Dr Narula’s May 2015 email to Purwar, the latter made the first breakthrough in developing the functional prototype . One of the biggest challenges the duo overcame was in creating a gene delivery vehicle. “We were initially trying to purchase it from abroad and they were asking for $3 million to produce it. We then decided to produce it at IIT-B,” Purwar says.
While the world and India were fighting the Covid-19 pandemic, Purwar, Dr Narula, and Dr Hasmukh Jain, the other principal investigator, were battling multiple challenges to ensure they met deadlines for the commercial launch they aimed for by the end of 2023.
“We were in the middle of constructing our laboratory at IIT-B when Covid-19 struck. The IIT administration’s timely approvals ensured that other certifications came in on time despite the pandemic,” Purwar says.
The second major challenge came when the Phase 1 trial coincided with the second wave of Covid-19. Dr Narula, principal investigator of paediatric Acute Lymphocytic Leukemia (ALL) care at TMH, and Dr Jain, principal investigator of the adult B-cell lymphoma study, started recruiting patients in early 2021. The trials were conducted at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), the research and development wing of TMH.
The commercial use of this therapy to treat certain blood cancers was approved by the Central Drugs Standard Control Organisation (CDSCO) in October. Dr Jain, who oversaw the multicentre Phase 1 and 2 pivotal clinical trial involving 60 r/r B-cell lymphoma and leukemia patients, says the therapy “has shown an excellent balance of efficacy and low-toxicity, which is a significant advantage in clinical management post- infusion, particularly in resource-constrained settings.”
As the team now busies themselves with presentations on the CAR T-cell therapy and Phase 2 trials among paediatric patients, they are yet to celebrate their achievement. “We achieved milestones at a socially awkward time. When we had time, we were engaged with other important things and by then, the moment to celebrate the milestone had passed. We intend to meet soon and celebrate,” laughs Dr Narula.
Purwar says his next aim is to make the treatment more accessible and affordable. “The current cost is ₹40 lakh. We want to bring it down by half. This is just the first CAR T-cell product. We will upgrade to more affordable versions.”
Purwar says research and development work on CAR T-cell therapy for solid tumours has begun too. “We are also looking at diversifying beyond oncology to look at autoimmune disorders, heart diseases and infectious diseases,” he adds.