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Table 1 Advantages and disadvantages of autologous and allogeneic CAR T cell therapies [49,50,51,52]

From: Donor T cells for CAR T cell therapy

Autologous CAR T cells

Allogeneic CAR T cells

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.