Tweaking genes to fight cancer: how does it work?

Context:

The United States federal food and drugs regulator had approved for the second time in less than seven weeks a new way to fight cancera type of gene therapy that turns cells in the patient’s body into a “living drug” that targets and kills cancer cells.

The two gene therapy products

  • Yescarta (axicabtagene ciloleucel) therapy, a way to fight cancer by an alteration of genes. The treatment, developed by Kite Pharma, a California-based biopharmaceutical company focussed on novel cancer immunotherapy products, is for adult patients with certain types of large B-cell lymphoma (DLBCL), who have not responded to or who have relapsed after at least two other kinds of treatment, USFDA said in its official release.
  • Kymriah (tisagenlecleucel) is for certain paediatric and young adult patients (up to 25 years of age) with a form of acute lymphoblastic leukemia (ALL), who had failed to respond to other types of treatments. ALL is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes.

Gene therapy for cancer:

  • Both Yescarta and Kymriah use ‘CAR-T cells’. CAR-T cell therapy works by helping the patient’s own immune system to fight cancer.
  • CAR stands for “chimeric antigen receptor” — engineered receptors that are grafted on to the patient’s ‘T cells’.
  • T cells are a type of lymphocytes (a kind of white blood cells) that destroy infected or cancerous cells. After their re-engineering in the lab, T cells are called CAR-T cells.
  • Once they are re-introduced into the patient’s bloodstream, the army of CAR-T cells multiplies, and goes after the cancer cells. Each dose of Kymriah or Yescarta is a customised treatment that is created using the individual patient’s own T cells.
  • Large B-cell lymphoma (DLBCL), which Yescarta fights, is a type of non-Hodgkin lymphoma (NHL). NHL is one of two types of lymphoma.
  • Lymphoma is a cancer of the lymphatic system, which is the network of tissues and organs that transports lymph, the fluid that contains infection-fighting WBCs.
  • The other kind of lymphoma is called Hodgkin lymphoma (HL), or Hodgkin disease. Both HL and NHL are cancers that start in WBCs called lymphocytes, but the specific kind of lymphocyte involved is different in each type of lymphoma.
  • NHL is the more common type of lymphoma. According to the worldwide Globocan 2012 report, the estimated incidence of NHL in India was 23,801 (age-standardised rate (world) of 2.2), just under three times the incidence of HL.
  • The age-standardised mortality rate (world) was 1.5. Neither is among the five most frequently occurring types of cancer in India.

Known risks in the treatment

Yescarta has the potential to cause severe side effects, and directed that patients must be informed of them before the therapy. Among potential complications are cytokine release syndrome (CRS), a response to the activation and proliferation of CAR-T cells, which leads to high fever and neurological problems.

Is this good news for India?

  • Anything new is costly, But it is new hope for India as well.
  • In India, CAR-T cells are being developed by Tata Memorial Hospital and IIT Bombay, along with the US National Cancer Institute.
  • Yescarta is meant to be infused into a vein, and must be manufactured individually for each patient. The cost will be $ 373,000 (over Rs 2.4 crore).
  • The country should focus on developing its own CAR-T cells, which is the only way forward; otherwise only those who have the reach and resources will be able to avail of these expensive therapies by going aboard.
  • Currently, experts say, patients with large B-cell lymphoma in second or later lines of therapy have poor outcomes since nearly half of them either do not respond, or relapse shortly after bone marrow transplants.
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