CAR T-cell Therapy — Cellular Immunotherapy

CAR T-cell therapy combines adoptive cellular therapy with genetic engineering principles. Peripheral blood mononuclear cells are collected from the patient via leukapheresis. In a dedicated manufacturing facility, viral vectors introduce recombinant genetic code into the patient's T cells, directing them to express chimeric antigen receptors consisting of an extracellular antibody-derived binding domain fused to intracellular T-cell signalling molecules.

Following lymphodepleting chemotherapy, the engineered CAR T cells are reinfused into the patient. Once back within the circulation, these specialised cells bind specifically to their cognate cell-surface antigens independent of major histocompatibility complex (MHC) presentation. This binding initiates robust intracellular signalling, promoting cytotoxic cell lysis, cytokine release, and rapid clonal expansion of the anti-tumour T-cell population.

CAR T-cell therapy represents a transformative option for patients whose blood cancers have relapsed or proved refractory to conventional treatments like chemotherapy or stem cell transplants. It is a highly complex, one-time living treatment that requires specialised administration in certified treatment centres. Being informed allows patients and carers to prepare for the logistics of cell collection, waiting windows, and the close inpatient monitoring needed to manage acute immunologic side effects safely.

Eligibility requires immunohistochemistry or flow cytometry confirming surface antigen expression on malignant cells, most commonly CD19 for lymphomas and leukaemias or B-cell maturation antigen (BCMA) for multiple myeloma. Post-infusion monitoring involves serial blood counts, quantitative polymerase chain reaction (qPCR) or flow cytometry to track CAR T-cell persistence, and cytokine profiling (such as IL-6, ferritin, and CRP) to detect early inflammatory toxicity.

CAR T-cell therapy is primarily approved for haematological malignancies. It is utilised extensively in treating relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, and multiple myeloma. Research is actively exploring expanding CAR T architectures to target antigens expressed in solid tumours.

Prior to infusion, patients receive short-course conditioning chemotherapy (typically fludarabine and cyclophosphamide) to deplete existing lymphocytes, creating an environment that supports CAR T-cell proliferation. Following infusion, patients are closely monitored for unique toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Managing these conditions promptly requires specialised protocols, including the IL-6 receptor antagonist tocilizumab and high-dose corticosteroids.