CAR T cell therapy

Introduction

CAR T cell therapy is a form of immunotherapy in which a patient’s own T lymphocytes are genetically engineered to better recognize and kill cancer cells (especially used in some types of non-Hodgkins lymphoma, relapsed or refractory B‑cell acute lymphoblastic leukemia and relapsed or refractory multiple myeloma )
CAR stands for chimeric antigen receptor, an engineered protein placed on the surface of T cells that allows them to bind a specific antigen on cancer cells (for example, CD19 on B‑cell malignancies)
T cells are first collected from the patient’s blood using apheresis, which separates white cells and returns the rest of the blood. In a specialized lab, a gene encoding the CAR is inserted into these T cells, which are then expanded over several weeks until there are enough cells for treatment
before infusion of CAR T cells, patients usually receive short-course lymphodepleting chemotherapy to reduce existing immune cells and improve expansion of the engineered cells.
the CAR T cells are then given back intravenously, typically over 30–60 minutes, after which they circulate, expand, and seek out cells expressing the target antigen throughout the body
when a CAR T cell binds its target antigen, it becomes activated, proliferates, and can directly kill the cancer cell while also releasing cytokines that recruit further immune responses

cytokine release syndrome (CRS)
- this is the most characteristic acute toxicity of CAR T cell Rx which often occurs as CAR T cells rapidly activate and expand
- it is a systemic inflammatory reaction causing fever, hypotension, and possible organ dysfunction
immune effector cell-associated neurotoxicity syndrome (ICANS)
- eg.confusion, difficulty speaking, or seizures
- typically appear days after the infusion
delayed CAR T-associated immune-related adverse events (CirAE)
- delayed effects which can happen weeks or even months after treatment
- increases 12 month mortality from non-relapse causes from ~3% to 17% in those with relapsed or refractory multiple myeloma given ciltacabtagene autoleuce ¹⁾
- delayed cranial nerve palsies
- Parkinson's disease-like symptoms
- sepsis from enterocolitis - can be fatal in those with compromised immune systems

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