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Content

• Background
• How it works?
• Advantages of CAR-T Cell therapy over other Cancer fighting methods
• CAR T-Cell Therapy in India
• Significance

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Background:

How Cancer has been treated before CAR T-Cell Therapy:

• Surgery (removing the cancer)
• Radiotherapy (delivering ionizing radiation to the tumour)
• Systematic Therapy (administering medicines that act on tumour)
  • The earliest form of systematic therapy was chemotherapy. It preferentially acts on cancer cells because of the latter’s rapid, unregulated growth and poor healing mechanisms. These drugs have modest response rate and significant side effects as they effect numerous cell types in the body.
  • The next stage in its evolution was targeted agents a.k.a. immunotherapy: The drugs bind to specific target on the cancer or in the immune cells that help the tumour grow or spread. This method often has less side effects as the impact on non-tumour cells is limited. However, it is effective only against tumours that express these targets.
• CAR-T Cell Therapy has emerged as a new development in this front.
  • It is a revolutionary therapy that modifies immune cells, specifically T-Cells, by turning them into potent cancer fighters known as CAR-T Cells.

How it works?

• • • In CAR T-cell therapy, the patient’s blood is drawn to harvest T-cells – immune cells that play a major role in destroying tumour cells.
    • Researchers modify these cells in the laboratory so that they express specific proteins on their surface, known as chimeric antigen receptors (CAR): they have an affinity for proteins on the surface of tumour cells. This modification in the cellular structure allows CAR T-cells to effectively bind to the tumour and destroy it.
    • These modified cells are then infused back into the patient’s blood stream after conditioning them to multiply more effectively.
    • The cells are even more specific than targeted agents and directly activate the patient’s immune system against cancer, making the treatment more clinically effective. This is why they are called ‘living drugs.

Advantages of CAR-T Cell therapy over other Cancer fighting methods:

• • It is very accurate and only targets cancer cells.
  • It makes the treatment easier with onetime therapy (unlike several sessions of chemotherapy)
  • It can also fight non-responsive cancer patients.
  • It is designed to cure and provide lifelong benefits.

CAR T-Cell Therapy in India:

• The first major clinical trial showing they were effective was published almost a decade ago. The first indigenously developed therapy in India was successfully performed only in 2021.
• In Oct 2023, the Central Drugs Standard Control Organization (CDSCO) granted market authorization for NexCAR19, India’s first indigenously developed CAR-T cell therapy, to ImmunoAct, a company incubated by IIT Bombay. This paves the way for commercial launch of this therapy in India.
• It is designed to target cancer cells that carry the CD19 protein. This protein acts like a flag on cancer cells, which allows CAR-T cells to recognize and attach themselves to the cancer cells and start process of elimination.
  • Who can get the NexCAR19 therapy?
    • The therapy is for people with B-Cell lymphomas who didn’t respond to standard treatments like chemotherapy, leading to relapse or reoccurrence of the cancer.
    • B-Cell leukaemia is most common among children. Are they also eligible?
      • For now, therapy’s approval is only for patients aged 15 years and above.
      • The pediatric trial phase is currently underway at the Tata Memorial Hospital, in collaboration with IIT-Bombay.

Significance:

• India is one of the first developing country to have its own Car-T therapy. Even some developed nations don’t have their own CAR-T therapies and they import from USA or
  Europe.
• This reduces the cost of treatment to about 1/10th of the cost abroad and has the potential of boosting medical tourism in India. It costs around Rs 3.3 crores abroad while in India it will cost somewhere between 30-40 lakh rupee.
• Lab and animal studies have shown that NexCAR19 lead to significantly lower drug-related toxicities. For e.g., it causes minimal damage to neurons and the central  nervous system, a condition known as neurotoxicity. The therapy also leads to minimal Cytokine Storm Syndrome (CRS), which is characterized by inflammation and hyperinflammation in the body due to the death of a significant number of tumour cells, as CAR-T cells are designed to target and eliminate cancer cells.

Practice Questions:

• Explain the mechanisms of CAR-T Cell therapy? Discuss the key advantages of NexCAR19 over other foreign CAR-T cell therapies [15 marks, 250 words