Chimeric Antigen Receptor-T (CAR-T) Cells as “Living Drugs”: A Clinical Pharmacist Perspective
Table 1
Autologous versus allogeneic CAR-T cell therapy [64].
Autologous
Allogeneic
Origin
Patient
Healthy donor
Production and manufacturing
Long lead time from leukapheresis to CAR-T cell administration Variability in the starting T cell product difficulty to control quality parameters Greater persistence of CAR-T cells
Scaled-up process allows the production of a greater number of products from a single donor “Off-the-shelf” availability Standardised processes Standardised HLA-matched batches
Slow disease progression Use of standard lymphodepletion regimens Successful manufacturing and expansion Absence of T cell paucity Previous lines of therapy
Rapid disease progression Use of enhanced lymphodepletion regimens Manufacturing failure due to T cell paucity or failed ex vivo expansion Autologous manufacturing logistic issues
Associated issues and risks
Frequent severe grade ≥3 CRS and ICANS CAR-related gene modifications Long-term side-effects such as B-cell aplasia with B-cell associated CAR-T cells Limited by the number of cells High cost
CRS CAR and/or gene-editing modifications GvHD Allo-rejection Toxicities related to enhanced lymphodepletion Reduced therapeutic efficiency upon standard lymphodepletion Shorter persistence Increased risk of alloimmunisation requiring redosing Moderate cost (expected)
