haEmatology and oncology
CAR T-cell therapy:
managing side effects
This article focuses on the most commonly observed toxicities observed in
patients treated with chimeric antigen receptor (CAR) T-cell therapy
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Tiene Bauters
PharmD PhD
Department of
Pharmacy, Department
of Pediatric Hematology,
Oncology and Stem Cell
Transplantation, Ghent
University Hospital,
Ghent, Belgium
For many years, chemotherapy, surgery and
radiotherapy have been the cornerstones of
cancer treatment. Due to the severe side effects of
traditional chemotherapy and radiotherapy, new
classes of targeted drugs including monoclonal
antibodies (for example, rituximab, cetuximab)
and small molecule drugs (for example, tyrosine
kinase inhibitors such as imatinib, dasatinib) have
been introduced. They target cancer cells by
homing in on specific molecular changes seen
primarily in those cells and allowing the
distinction between potentially harmful cells and
healthy cells. These agents are ideally only toxic
to the cells identified as harmful. Compared with
conventional chemotherapy, they are usually less
toxic and more comfortable for the patient. 1,2
Many targeted therapies, including monoclonal
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antibodies (mAbs), non-specific immunotherapies,
T-cell therapy, oncolytic virus therapy, and cancer
vaccines use the patient’s immune system to fight
the disease. Although immunotherapy has
provided many new therapeutic approaches,
cancer treatment still remains a challenge,
especially in cases of failure or resistance to
therapies. Patients with haematologic
malignancies, for example, often have a poor
prognosis in cases of disease progression after
primary and secondary therapies. Novel
treatment options are needed for patients who
have failed multiple lines of chemotherapy. 1,2
Whereas conventional cytotoxic drugs cause
adverse events and toxicities by compromising
defence mechanisms, immunotherapy may
induce serious overwhelming inflammatory
responses and auto-immunity, thereby
complicating their use. 1,2 Several types of
immunotherapy are under study in clinical trials
to determine their effectiveness in treating
various types of cancer, or have recently been
licensed: one such type is chimeric antigen
receptor (CAR) T-cell therapy.
Basis of CAR-T therapy
T-cells can be genetically modified to express
CARs. These are fusion proteins containing both
an antigen recognition moiety and T-cell
activation domains. 3–5
CAR T-cell therapy starts with the collection of
T-cells from the patient. This is performed by
apheresis and the cells are re-engineered in a
laboratory where they are genetically engineered
to produce CARs on their surface. These modified
cells, known as CAR T-cells, allow the T-cells to
recognise an antigen on targeted tumour cells.
These re-engineered CAR T-cells are then
multiplied and the number of genetically
modified T-cells expanded by laboratory cell
culture. The CAR T-cells are consequently frozen
and, when there are sufficient quantities, are
infused into the patient. The engineered immune
cells recognise targets with high precision and
have the potential to decrease the non-selective
toxicity that is observed with conventional
chemotherapeutics. 2,4
So far, CAR T-cells targeting the CD19 antigen
on B-cells have been used successfully in relapsed
or chemotherapy-refractory acute lymphoblastic
leukaemia, chronic lymphocytic leukaemia, and
non-Hodgkin lymphoma. CAR T-cells can produce
durable remissions in haematological