Explainer: How CAR-T cell therapy engineers immune cells to treat cancer

Hyderabad: CAR-T cell therapy is a revolutionary treatment approach to treat advanced or complicated blood cancers which conventionally available treatments couldn’t remedy.

How do CAR-T cell therapies treat cancer?

CAR-T cell therapies are biological drugs.

Extracting T-cells: The therapy involves extracting immune cells called T-lymphocytes from the patient’s body and then re-programming them to engage specific targets on the surfaces of certain cancer cells.

Re-programming T-cells: The re-programming is performed with the help of a safe vehicle called a viral vector, which is genetically modified to confer certain fixed properties to the cells.

Cancer cells targeted: Chimeric Antigen Receptors (CARs) are then expressed on the surfaces of T-cells. These cells are grown in a laboratory setting to a desirable dose and injected into the patient so that they identify the cancer cells and eventually destroy them.

Globally approved CAR-T cell therapies target either the CD19 antigen, present in certain B-cell Non-Hodgkin’s Lymphomas (B-NHLs) and B-cell Lymphoblastic Leukaemia or BCMA present in Multiple Myeloma.

What is the treatment procedure in CAR-T cell therapies?

Treatment with CAR-T involves three major steps:

Leukapheresis: This is the process of collection of white blood cells performed at the treatment centre/hospital. Leukapheresis is a day-care procedure and usually requires 2-3 hours.

Interim period: CAR-T cells are usually manufactured within three weeks of the shipment of the Leukapheresis sample. In the interim period, the oncologist may administer a Bridging Therapy to lower the patient’s disease burden. Approximately five days before CAR-T cell infusion, the patient will start receiving a Conditioning Chemotherapy so that his/her body is ready for CAR-T cell infusion.

Infusion: CAR-T cells are infused as an in-patient procedure. The patient may be hospitalised for ~7-15 days to monitor and manage side effects, based on the physician’s discretion. The patient may experience fever, muscle ache, dizziness, breathing difficulty and tiredness within the first 2-3 weeks from the infusion and may receive medications if required, to manage these symptoms.

Countries where CAR-T cell therapies can be obtained

Six such CD19-directed or BCMA-targeting CAR-T cell therapies are approved in several Western countries. Some are approved regionally in countries such as China and Israel. Beyond these blood cancers, several CAR-Ts and other genetically modified cell therapies are being developed to treat solid and connective tissue cancers.

Apollo Cancer Centers in Visakhapatnam has introduced CAR-T cell therapy for the first time in Andhra Pradesh.

In India, the first commercially approved CAR-T cell therapy is NexCAR19™.

It targets CD19 and is approved for the treatment of patients aged 15 years and above with B-cell Non-Hodgkin’s Lymphomas and B-cell Acute Lymphoblastic Leukaemia (B-ALL).

It was developed by IIT-Bombay and its spin-off company ImmunoACT and was clinically steered by Tata Memorial Centre. Another CAR-T cell therapy developed by IDIBAPS in Barcelona in partnership with Immuneel Therapeutics in Bengaluru has also been recently approved for B-NHLs.

CAR-T cell therapy at Apollo Hospitals

CAR-T cell therapy is available in Apollo Cancer Centers in Visakhapatnam.

As one of the earliest adopters of this treatment across India, in partnership with the Immuno Act, Apollo Cancer Centers in Vizag was able to bring cutting-edge cellular therapy to Andhra Pradesh. With this pioneering effort patients with hitherto dismal scenarios got a fresh lease of life.

What is the right time to administer CAR-T cell therapy?

Results in CAR-T cell therapies may depend on a number of factors including the burden and nature of the disease, when and which prior treatments were administered, and whether the therapy was administered earlier or later in the line of treatment.

Generally, in B-cell cancers, a remission that persists for five years or more is considered a functional cure.

Overall, results vary with every CAR-T cell therapy but the chances of survival without progression of the disease are generally higher than 40 per cent over three years based on available data from globally approved CAR-T cell therapies. With Indian CAR-T cell therapies, the data is still young and will mature in time

Are there any side effects to CAR-T cell therapy?

CAR-T cell therapy involves some known side-effects called Cytokine Release Syndrome (CRS), Macrophage Activation Syndrome (MAS/HLH) and Immune-cell Effector-Associated Neurotoxicity (ICANS), in which the patient may experience symptoms such as fever, nausea, tiredness, chills, confusion, and in rare cases severe infection and seizures.

These are usually resolved within 7-15 days of hospitalisation post-infusion.

In summary, CAR-T cell therapy represents a landmark advancement in blood cancer treatment. The future is bright, where cellular therapies are likely to foray big time into advanced solid organ cancers also.