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Success of CAR-T cell therapy

Context:

The NexCAR 19, is an indigenously developed therapy was administered to 15 patients in India. Three of them have successfully achieved cancer remission. The commercial use of this therapy was approved by the Central Drugs Standard Control Organisation (CDSCO) in October 2023.

Relevance:

GS III: Science and Technology

Dimensions of the Article:

  1. About Cancer
  2. Evolution of Systemic Therapy
  3. CAR T-cell Therapy

About Cancer

  • Cancer is a widely feared disease that leads to many deaths globally, including in India where more than a million people suffer from it annually.
  • The mechanisms behind the development, treatment and control of cancer have been extensively studied in the field of biology and medicine.
  • In healthy individuals, cell growth and differentiation are tightly controlled, but in cancer, these regulatory mechanisms break down.
  • Normal cells have a property called contact inhibition, which prevents them from growing uncontrollably when in contact with other cells.
  • However, cancer cells appear to lose this property, leading to the uncontrolled growth and division of cells, resulting in tumors.

Types of Tumors

  • Tumors are of two types:
    • Benign 
    • Malignant
  • Benign tumors normally remain confined to their original location and do not spread to other parts of the body and cause little damage.
  • The malignant tumors, on the other hand are a mass of proliferating cells called neoplastic or tumor cells. These cells grow very rapidly, invading and damaging the surrounding normal tissues.

Causes of Cancer

  • Cancer is caused by the transformation of normal cells into cancerous neoplastic cells. This transformation can be triggered by physical, chemical or biological agents called carcinogens.
  • These agents include ionizing radiations such as X-rays and gamma rays, non-ionizing radiations such as UV rays, and chemical carcinogens found in tobacco smoke.
  • Cancer-causing viruses, known as oncogenic viruses, also have genes called viral oncogenes that can contribute to the development of cancer.
  • Additionally, certain genes called cellular oncogenes or proto oncogenes in normal cells can be activated under certain conditions, resulting in the oncogenic transformation of cells.

Three major forms of treatment

  • The three major forms of treatment for any cancer are surgery (removing the cancer), radiotherapy (delivering ionising radiation to the tumour), and systemic therapy (administering medicines that act on the tumour).
  • Surgery and radiotherapy have been refined significantly over time whereas advances in systemic therapy have been unparalleled.

Evolution of Systemic Therapy

Early Stage: Chemotherapy

  • Chemotherapy was the earliest form of systemic therapy, acting preferentially on cancer cells due to their rapid growth and poor healing mechanisms.
  • The response rate was modest and side-effects significant as the drugs affected numerous cell types in the body.

Next Stage: Targeted Agents (Immunotherapy)

  • Targeted agents, also known as immunotherapy, involved drugs that bind to specific targets on cancer cells or immune cells that help the tumor grow or spread.
  • This method had fewer side-effects as the impact on non-tumor cells was limited, but was effective only against tumors that expressed these targets.

CAR T-cell Therapy

Chimeric antigen receptor (CAR) T-cell therapies use a patient’s own cells that have been modified in a laboratory to attack tumors.

Process:

  • Blood is drawn from the patient to harvest T-cells.
  • The T-cells are modified in the laboratory to express chimeric antigen receptors (CAR) that have an affinity for proteins on the surface of tumor cells.
  • The modified cells are infused back into the patient’s bloodstream after being conditioned to multiply more effectively.
  • The CAR T-cells bind to the tumor and destroy it, with the patient’s immune system clearing the debris.

Advantages:

  • More clinically effective than chemotherapy or immunotherapy as it directly activates the patient’s immune system against cancer.
  • More specific than targeted agents as it uses the patient’s own cells.
  • Considered as “living drugs”.

Where is it used?

  • Currently approved for treating leukaemias and lymphomas
  • Used among patients with cancers that have returned after initial treatment or not responded to previous chemotherapy or immunotherapy
  • Efficacy varies, with response rate as high as 90% in certain kinds of leukaemias and lymphomas and significantly lower in other types of cancers

Challenges:

  • Complex preparation process
  • First clinical trial demonstrating effectiveness published almost a decade ago
  • Requires technical and human resources to administer, with treatments in the U.S. costing more than a million dollars
  • Significance potential side-effects such as cytokine release syndrome and neurological symptoms

What are ‘cell therapies’?

  • Cell therapies are a form of cancer treatment that involves using a patient’s own cells.
  • One form of cell therapy is CAR T-cell therapy, which modifies T-cells to attack cancer cells and has been approved for certain types of leukemia and lymphoma.
  • The treatment is complex and expensive, but has shown high response rates in certain cancers.
  • Cell therapies also have potential to help understand the complexities of cancer and offer new treatments, including personalised anti-cancer vaccines and tumour infiltrating lymphocyte therapies.
  • Despite the challenges, the field holds promise for developing more sophisticated cancer treatments with fewer side-effects.

-Source: The Hindu, the Indian Express


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