Relapsed or refractory aggressive B-cell lymphoma has an extremely poor 
prognosis and efforts to develop novel therapies for these patients have failed 
for almost four decades until the advent of chimeric antigen receptor (CAR) 
T-cell therapy. Within the last one year, two anti-CD19 CAR T-cell therapy 
products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the 
United States Food and Drug Administration for the treatment of relapsed or 
refractory large B-cell lymphoma after at least two lines of systemic therapy 
based on multicenter single-arm phase two clinical trials. Here, we will discuss 
the different components of the CAR construct and their mechanisms of action, 
the role of conditioning chemotherapy, the efficacy and toxicity observed with 
anti-CD19 CAR T-cell therapies in aggressive B-cell lymphomas, and emerging 
strategies to further improve the safety and efficacy of these highly promising 
approaches.