A living drug: application of CAR-T therapy for lymphoid malignancies and beyond

Abstract

The ongoing development of novel personalized cancer therapies has resulted in the implementation of T cells enriched with synthetic chimeric antigen receptors, known as chimeric antigen receptors T cell (CAR-T) cells, into clinical practice. CAR-T cells are able to recognize and bind specific antigens present on the surface of target cells — so-called tumor-associated antigens. This innovative method has been approved for the treatment of hematological malignancies and may also serve as a bridge to hematopoietic stem cell transplantation. The production of the drug containing modified T cells consists of several steps — leukapheresis, T cell activation, transduction and expansion of the final CAR-T cells. Activation of CAR-T cells occurs through a pathway independent of the major histocompatibility complex, which is often associated with uncontrolled responses from the immune system and adverse reactions such as cytokine release syndrome. CAR-T therapy can only be performed in certified centers, and requires close cooperation between experienced specialists of different medical disciplines. This is what determines its effectiveness. Every step from collection and cryopreservation, through transport and modification, to thawing and infusion is strictly controlled because it has a critical impact on the quality and efficiency of the drug. Despite its proven benefits, CAR-T therapy remains available only to patients who meet well-defined criteria. These however are liable to change with the emergence of new indications.