Persistence and efficacy of second generation CAR T Cell against the LeY Antigen in acute myeloid leukemia Academic Article uri icon

abstract

  • In a phase I study of autologous chimeric antigen receptor (CAR) anti-LeY T-cell therapy of acute myeloid leukemia (AML), we examined the safety and postinfusion persistence of adoptively transferred T cells. Following fludarabine-containing preconditioning, four patients received up to 1.3 × 109 total T cells, of which 14-38% expressed the CAR. Grade 3 or 4 toxicity was not observed. One patient achieved a cytogenetic remission whereas another with active leukemia had a reduction in peripheral blood (PB) blasts and a third showed a protracted remission. Using an aliquot of In111-labeled CAR T cells, we demonstrated trafficking to the bone marrow (BM) in those patients with the greatest clinical benefit. Furthermore, in a patient with leukemia cutis, CAR T cells infiltrated proven sites of disease. Serial PCR of PB and BM for the LeY transgene demonstrated that infused CAR T cells persisted for up to 10 months. Our study supports the feasibility and safety of CAR-T-cell therapy in high-risk AML, and demonstrates durable in vivo persistence.

authors

  • Ritchie, DS
  • Neeson, PJ
  • Khot, A
  • Peinert, S
  • Tai, T
  • Tainton, K
  • Chen, K
  • Shin, M
  • Wall, DM
  • Hönemann, D
  • Gambell, P
  • Westerman, DA
  • Haurat, J
  • Westwood, JA
  • Scott, AM
  • Kravets, L
  • Dickinson, M
  • Trapani, JA
  • Smyth, MJ
  • Darcy, PK
  • Kershaw, MH
  • Prince, HM

publication date

  • 2013