KYMRIAH® (Tisagenlecleucel) is an autologous T-cell prescription cancer treatment used in patients up to 25 years old who have B-cell acute lymphoblastic leukaemia (ALL) that is either relapsing or refractory.
The therapy involves reprogramming the patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing cells.
Un-mobilized Leukapheresis is collected from the leukemia patients and subsequently cryopreserved and sent to Novartis for manufacturing of CAR T-cells.
In order to protect the cells from damage and to maximise viability, the product is mixed with a cryoprotectant freezing medium containing dimethyl sulphoxide (DMSO) and human albumin solution (4.5%) (1:4). DMSO enters the cells rapidly, excludes water and prevents the formation of ice crystals within the cells which can cause cell death and destruction of cell organelles upon thawing.
Cell products are ordinarily passive frozen in a -80°c, however, as part of Kymriah’s quality assurance, Novartis require a controlled rate decrease from 4°c of -1°c/min until -40°c followed by -10°c/min until -80°c.
The controlled rate freezer (CRF) program was validated with 3 runs (1x Human Albumin Solution, 2 x Healthy Donor HPC-A). Cell recovery, viability and functionality were compared between the pre and post cryopreservation by CD3 count and viability and PHA cell proliferation assay. An acceptance criterion of within 10% variation was set in order to approve the change to procedure.
To date 12 patients have had T-Cells cryopreserved via this CRF procedure, with consistently positive levels of CD3 recovery, viability and functionality.
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