Autologous, patient-specific chimeric antigen receptor T-cell (CART) therapy has 
emerged as a powerful and potentially curative therapy for cancer, especially 
for CD19-positive hematological malignancies. Indeed, on August 30, 2017, the 
University of Pennsylvania-designed CD19-directed CART (CART-19) cell therapy 
(CTL019, tisagenlecleucel-t, Kymriah - Novartis) became the first CART therapy 
approved by the Food and Drug Administration (FDA) for acute lymphoblastic 
leukemia. However, the development of CART technology and its wider application 
is partly limited by the patient-specific nature of such a platform and by the 
time required for manufacturing. The efficacious generation of universal 
allogeneic CART cells would overcome these limitations and represent a major 
advance in the field. However, several obstacles in the generation of universal 
CART cells need to be overcome, namely the risk of CART rejection and the risk 
of graft-versus-host disease mediated by the allogeneic CART. In this review, we 
discuss the different strategies being employed to generate universal CART and 
provide our perspective on the successful development of a truly off-the-shelf 
CART product.