Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia

C. Quintarelli, S. Sivori, S. Caruso, S. Carlomagno, M. Falco, I. Boffa, D. Orlando, M. Guercio, Z. Abbaszadeh, M. Sinibaldi, S. Di Cecca, A. Camera, B. Cembrola, A. Pitisci, M. Andreani, L. Vinti, S. Gattari, F. Del Bufalo, M. Algeri, G. Li PiraA. Moseley, B. De Angelis, L. Moretta, F. Locatelli

Research output: Contribution to journalArticlepeer-review

Abstract

We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective “off-the-shelf” immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.

Original languageEnglish
Pages (from-to)1102-1115
Number of pages14
JournalLeukemia
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 2020

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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