CAR T Cell Therapy and Its Cardiovascular Effects

What is CAR T Cell Therapy?

Chimeric antigen receptor or CAR T is used in T cell treatment, a recombinant protein fusion that can activate T cells to detect a particular antigen and kill the cell. This novel approach of immunotherapy targets cancer cells with T cells that have undergone specific modifications. Our immune systems can be strengthened to fend off cancer and safeguard our bodies.

 

The CD19-specific CAR T is the first extremely effective treatment. This is why large B-cell lymphoma, multiple myeloma, or acute B-cell lymphoblastic leukemia have been particularly responsive to and refractory to CAR T cell therapy.

How is CAR T Cell Therapy Performed?

The patient’s T cell lymphocytes are taken from them and genetically altered in the lab such that they now detect tumor cells. Before being given back to the same patient via a single intravenous infusion, the CAR T cells rapidly multiply in the lab to produce therapeutic amounts. It is typically necessary to provide chemotherapy to lower the patient’s lymphocyte count to prepare them for CAR T cell therapy. The FDA has approved several CAR T cell treatments: Breyanzy, Kymriah, Tecartus, and Yescarta, while several other treatments are under investigation.

How Effective Are the Present CAR T Cell Therapies?

Tumor resistance to single antigen-targeting CAR designs is one of the most difficult restrictions of CAR-T cell treatment. Although CAR-T cells that target a single antigen can initially produce excellent response rates, a sizable fraction of patients who receive treatment with these CAR-T cells may have malignant cells that exhibit either partial or complete loss of target antigen expression. 

ALL patients show stable answers to CD19-targeted CAR-T cell treatment. Recent follow-up data suggest developing a common disease resistance mechanism, including downregulation/loss of CD19 antigen in 30–70% of patients with recurrent disease after treatment. 

 

Cytokine Release Syndrome (CRS) as a Side Impact of CAR T Cell Therapy

A significant side effect of any immunotherapy, including CAR T cell therapy, is cytokine release syndrome (CRS).  Cytokines are small proteins essential in cell signaling and include growth factors, Interferon, and Interleukins (IL-6) involved in inflammation.

 

The signs and symptoms of CRS can range from moderate constitutional symptoms, including weariness, fever, and flu-like illness, to severe and life-threatening hypotension and hypoxia, which can cause confusion, fast breathing, collapse, and death.

 

The amount of CAR T cells injected and the severity of the underlying disease affect how severe the syndrome is. It typically happens five to six days following the infusion and has four clinical stages:

1: simply a fever

2: slight hypotension, hypoxia, and fever (requiring O2 nasal cannula)

3: fever, pressor-dependent hypotension, and hypoxia on more than 6 liters O2

4: fever, severe hypoxia requiring supplemental oxygen, and hypotension requiring repeated pressors.

Possible Side Effects of Cell Therapy

Cytokine-Release Syndrome (CRS). CRS symptoms can vary from mild flulike signs that include

• Nausea
• Fatigue
• Headache
• Chills
• Fever

The signs of CRS can also be more serious such as

• Low blood pressure
• Tachycardia (abnormally rapid heart rate)
• Capillary leakage (fluid and proteins spreading out of tiny blood vessels and pouring into surrounding tissues, resulting in dangerously lower blood stress)
• Cardiac arrest
• Cardiac arrhythmias
• Cardiac failure
• Hypoxia (lack of oxygen reaching the tissue)
• Renal insufficiency (poor function of the kidneys)
• Poor lung oxygenation
• Multiple organ failure
• Neurological symptoms (see below)

Severe CRS requires intensive care treatment.  Deaths have lived reported in CAR-T cell therapy practices.

Depending on the patient and the CAR T enclosures, CRS may appear within 1 to 21 days of CAR T-cell information. The duration of CRS is variable and depends on the type of intervention used to manage it.