| Manufacture is complex and expensive with variability in starting material (patient T cells) and resulting CAR T cell product. Limited T cell quality and quantity (autologous PBMCs from leukapheresis product) with risk of manufacture failure for heavily pre-treated patients (lymphopenia). |
Standardized manufacture with high quality starting material (healthy donor T cells) and high quality CAR T cell product. Multiple T cell sources from many healthy donors (PB or UCB). |
| Low scalability (1 product per patient) with increased time to treatment and production costs due to manufacture and quality control specific for individual patient. |
High scalability (1 product for many patients) with “off-the-shelf” bank of CAR T cell products, readily available (decreased time to treatment). Reduced production costs with manufacture and quality control applicable to many patients. |
| Risk of contamination with malignant cells in patient blood. |
Minimal risks of malignant cell contamination since T cells are sourced from healthy donor blood. |
| Limited optimization of T cell phenotype and function with limited editable cancer targets, promising applications in B cell malignancies but limited applications in T cell malignancies. |
High optimization of T cell phenotype and function to improve CAR T efficacy with multiple editable cancer targets, e.g. promising applications in both B and T cell malignancies. |
| Limited potency of CAR T cell product due to chemotherapy-treated patient T cells being more differentiated with lower proliferative capacity and rapid exhaustion. Increased in vivo persistence compared with allogeneic CAR T cells due to lack of immune rejection from the host. |
Potent CAR T cell product from healthy donor T cells, but with decreased in vivo persistence due to higher immunogenecity (from the host against infused CAR T cells). |
| CRS or CRES toxicities. Low immunogenicity and minimal risk of alloreactivity or immune rejection affecting clinical outcomes. |
CRS or CRES toxicities. Risk of alloreactivity factors (e.g. GVHD, immune rejection) affecting clinical outcomes. |
