Crafted in Indian labs, NexCAR19 takes India to next level in cancer care

Crafted in Indian labs, NexCAR19 takes India to next level in cancer care

Subject: Science and tech

Section: Health

NexCar19:

• NexCar19 is a type of CAR-T and gene therapy developed indigenously in India by ImmunoACT, which is a company incubated at IIT Bombay.
  • It is designed to target cancer cells that carry the CD19 protein.
• CAR-T therapy modifies a patient’s T cells to attack cancer cells, had already been launched in the US but was prohibitively expensive, costing up to ₹4 crores excluding additional hospitalization costs.

How are CAR-T cells made?

• CAR-T cells are created by collecting T-cells, a type of white blood cell, from a patient using a procedure known as leukapheresis. These T-cells are then genetically modified in a laboratory to express chimeric antigen receptors (CARs).
• This modification involves inserting a synthetically developed gene that codes for the CAR into the T-cells using viral vectors, commonly lentiviral vectors. After the modification, these engineered T-cells are cultured in the lab to increase their number into the millions. These cells are then returned to the hospital and infused into the patient, who typically undergoes chemotherapy prior to this infusion to improve the effectiveness of the therapy.
• The structure of a CAR includes both an external segment, which is composed of antibody fragments specifically chosen to target cancer cell antigens, and an internal segment responsible for initiating cellular signaling once the CAR binds to an antigen.
• This dual structure enables the CAR-T cells to recognize and attack cancer cells effectively. Notably, while similar therapies in the US use murine-derived antibodies, NexCAR19 includes human proteins alongside mouse antibodies, creating a ‘humanized’ CAR that potentially reduces toxicity.
• To date, the FDA has approved six CAR-T cell therapies, with four targeting CD19, a marker found on certain leukemia and lymphoma cells. NexCAR19 follows this target approach but stands out due to its humanized antibody design.

Collaboration with National Cancer Institute (NCI):

• The team sought expertise from the National Cancer Institute (NCI), enhancing their approach through insights gained at a conference hosted by the American Association for Cancer Research (AACR).
• By October 2023, the team achieved a major milestone when CDSCO approved the therapy for treating relapsed or refractory B-lymphomas and B-Acute Lymphoblastic Leukemia (B-ALL) after other treatments had failed.
• This accomplishment marked the emergence of a Made-in-India CAR-T cell therapy, a testament to the team’s commitment and the impactful collaboration with NCI.

Risks of CAR-T cell therapy:

• The most common side effect is cytokine release syndrome (CRS), an intense inflammatory response that can lead to severe complications.
• Neurotoxicity, infections, and low blood cell counts are also potential side effects, although the early clinical trials using ‘humanized’ antibodies in NexCAR19 did not report neurotoxicity.
• Despite its efficacy, the cost of CAR-T therapy remains a barrier.
  • NexCAR19, developed to be more affordable than its US counterparts, still costs between ₹40 to 45 lakh, making it one of the most expensive cancer treatments available.
  • Factors influencing the cost include labor, logistics, materials, facility expenses, and the costs associated with marketing, distribution, and intellectual property.

Source: TH