Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR‐T containing either CD28 or 4‐1BB

Abstract T cells modified with anti‐ CD 19 chimeric antigen receptor ( CAR ) containing either CD 28 or 4‐1 BB (also termed TNFRSF 9, CD 137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia ( ALL ). However, the difference between CD 28 and 4‐1 BB costimulatory signalling in CAR ‐T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD 19 CAR ‐T. The first 5 patients were treated with CD 28‐ CAR and the other 5 patients were treated with 4‐1 BB CAR ‐T. All the 10 patients were response‐evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD 28‐ CAR ‐T treatment. In the 4‐1 BB CAR ‐T treatment group, 3 patients achieved complete remission. Furthermore, FLT ‐3 ligand ( FLT 3 LG ) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD 28 CAR ‐T and 4‐1 BB CAR ‐T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune‐suppressive factor level.