CAR-T 治疗在血液学诊疗中的当前作用

CAR-T therapy based on the genetic modification of T-lymphocyte receptors is currently a rapidly expanding modern method of treatment of hematological malignancies. In this chapter, the authors review the history of the development of this kind of therapy, principles of the CAR-T therapy product manufacturing, and indications for the use of registered CAR-T therapy products. They also review the perspectives for the expansion of indications using this treatment on the basis of analysis of approved clinical trials. The need for the establishment of effective logistics pathways and the benefits of cryopreservation at different manufacturing steps are reviewed as well.

During their 2-year experience, the authors established a system of fluent cooperation between the local licensed Tissue Establishment (TE), CAR-T therapy product manufacturers, the Hospital Pharmacy, and a certified clinical CAR-T therapy centre. The leukapheresis of starting material, its processing, storage, and release for the manufacture took place in the authorized TE.

The starting material is usually fresh mature peripheral blood mononuclear cell concentrate, which is sent to the manufacturing site in a chilled (or sometimes cryopreserved) state and the final registered product is sent back in a frozen state. Individual manufacturers use different cold chains. Sometimes the starting material is frozen by the manufacturer and the final manufacture is carried out before the actual administration to the patient as a fresh suspension.

However, the most common variant used in registered products is the supply of the final product to the place of the administration in the cryopreserved state. Receipt of final products in the hospital cryobank attached to the TE takes place in cooperation between the TE staff with representatives of the Hospital Pharmacy and is followed by storage in a vapour phase of liquid nitrogen in a separate GMP-compliant container used exclusively for the storage of registered and investigational CAR-T therapy products at a temperature below -150 C.

Before the transport to the Clinical Department, the chain of recipient identity is checked, then the product is transported to the Clinical Department in a dry shipper at temperature below -150 C. After the second check in the presence of the clinical hematologists, the product is thawed and immediately infused. In the case of the use of investigational products, special attention is paid to meeting specific genetic safety rules in the regimen of genetically modified organisms.