CAR T-Cell Therapy

CAR-T cell therapy, short for Chimeric Antigen Receptor T-cell therapy, is a cutting-edge form of personalised immunotherapy used primarily to treat certain types of blood cancers like leukemia, lymphoma, and multiple myeloma. Here’s a breakdown of how it works and why it’s so promising:

What Is CAR-T Cell Therapy?

CAR-T therapy involves genetically modifying a patient’s own T cells (a type of white blood cell that plays a key role in the immune system) to better recognize and attack cancer cells.

How It Works — Step-by-Step

T Cell Collection
Blood is drawn from the patient, and T cells are separated out through a process called leukapheresis.
Genetic Engineering
In a lab, a synthetic gene is inserted into these T cells. This gene encodes a chimeric antigen receptor (CAR) — a special receptor that allows the T cells to recognize specific proteins (antigens) on cancer cells.
Cell Expansion
The modified CAR-T cells are multiplied until there are millions to billions of them.
Preconditioning Chemotherapy
Before infusion, the patient receives chemotherapy to reduce other immune cells and make room for the CAR-T cells.
Infusion
The engineered CAR-T cells are infused back into the patient’s bloodstream.
Immune Attack
These CAR-T cells now patrol the body, seek out cancer cells, bind to them via the CAR, and destroy them.

What Makes It Special?

Precision Targeting: CAR-T cells are designed to recognise specific antigens found only on cancer cells, minimising damage to healthy cells.
Living Drug: Since the therapy uses the patient’s own cells, it’s often referred to as a “living drug.”
Potential for Cure: In some cases, CAR-T therapy has led to complete remission, even in patients with advanced or treatment-resistant cancers.

Approved Uses

CAR-T therapy is currently approved for:

B-cell acute lymphoblastic leukemia (ALL)
Diffuse large B-cell lymphoma
Follicular lymphoma
Multiple myeloma
And other high-grade B-cell lymphomas.

CAR T-cell therapies for adults and children

More than 80% of children diagnosed with ALL that arises in B cells are cured by intensive chemotherapy. But for many years there were no effective treatments for children whose cancers returned, or relapsed, after chemotherapy or a stem cell transplant.

FDA-Approved CAR T-cell Therapies :

CAR T-Cell Therapy	Approved Use(s)
Abecma (ide-cel)	Multiple myeloma
Aucatzyl (obe-cel)	B-cell ALL (adult)
Breyanzi (liso-cel)	Follicular lymphomaLarge B-cell lymphomaMantle cell lymphomaChronic lymphocytic leukemia
Carvykti (cilta-cel)	Multiple myeloma
Kymriah (tisa-cel)	B-cell ALL (pediatric/young adult)Diffuse Large B-cell LymphomaFollicular lymphoma
Tecartus (brexu-cel)	B-cell ALL (adult)Mantle cell lymphoma
Yescarta (axi-cel)	Large B-cell lymphomaFollicular lymphoma

The timeline of milestones in CAR-T cell development

Signal Transduction and Targeted Therapy (Sig Transduct Target Ther) ISSN 2059-3635 (online)

The first reports published in scientific journals or conference abstracts, excluding patent applications, are highlighted. The efficacy of CD19 CAR-T cells was reported in patients with B-NHL in 2010, CLL in 2011, and B-ALL in 2013.

The figure was created using Biorender.com by Nature.com – Credit

Risks & Side Effects

CAR T-cell therapy can be very effective against some types of hard-to-treat cancers, but it can also sometimes cause serious or even life-threatening side effects. Because of this, it needs to be given in a medical center specially trained in its use, and you will need to be watched closely for several weeks after getting the CAR T cells.

Cytokine Release Syndrome (CRS): A potentially severe immune reaction.
Neurological effects: Confusion, seizures, or encephalopathy.
Infections: Due to immune suppression.

Cytokine release syndrome (CRS)

As CAR T cells multiply, they can release large amounts of chemicals called cytokines into the blood, which can ramp up the immune system. Serious side effects from this release can include:

High fever and chills
Trouble breathing
Severe nausea, vomiting, and/or diarrhea
Feeling dizzy or lightheaded
Headaches
Fast heartbeat
Feeling very tired

As doctors are gaining more experience with CAR T-cell therapy, they are learning how to recognize CRS early, as well as how to treat it.

Nervous system problems

This treatment can sometimes have serious effects on the nervous system, leading to a condition called immune effector cell-associated neurotoxicity syndrome (ICANS). This can result in symptoms such as:

Headaches
Changes in consciousness (awake easily or hard to awaken)
Confusion or agitation
Seizures
Shaking or twitching (tremors)
Trouble speaking and understanding
Loss of balance

Because of the risk of these side effects, you’ll likely be told not to drive, operate heavy machinery, or do any other potentially dangerous activities for at least 8 weeks after getting treatment.

Other serious side effects

Other possible serious side effects of CAR T-cell therapy can include:

Allergic reactions during the infusion
Abnormal levels of minerals in the blood, such as low potassium, sodium, or phosphorous levels
A weakened immune system, with an increased risk of serious infections
Low blood cell counts, which can increase the risk of infections, fatigue, and bruising or bleeding
Increased risk of second cancers