In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor

Greta Maria Paola Giordano Attianese, Virna Marin, Valentina Hoyos, Barbara Savoldo, Irene Pizzitola, Sarah Tettamanti, Valentina Agostoni, Matteo Parma, Maurilio Ponzoni, Maria T S Bertilaccio, Paolo Ghia, Andrea Biondi, Gianpietro Dotti, Ettore Biagi

Research output: Contribution to journalArticle

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by an accumulation of mature CD19+CD5+CD20dim B lymphocytes that typically express the B-cell activation marker CD23. In the present study, we cloned and expressed in T lymphocytes a novel chimeric antigen receptor (CAR) targeting the CD23 antigen (CD23.CAR). CD23.CAR+ T cells showed specific cytotoxic activity against CD23+ tumor cell lines (average lysis 42%) and primary CD23+ CLL cells (average lysis 58%). This effect was obtained without significant toxicity against normal B lymphocytes, in contrast to CARs targeting CD19 or CD20 antigens, which are also expressed physiologically by normal B lymphocytes. Moreover, CLL-derived CD23.CAR + T cells released inflammatory cytokines (1445-fold more TNF-β, 20-fold more TNF-α, and 4-fold more IFN-γ). IL-2 was also produced (average release 2681 pg/mL) and sustained the antigen-dependent proliferation of CD23.CAR+ T cells. Redirected T cells were also effective in vivo in a CLL Rag2-/-γc-/- xenograft mouse model. Compared with mice treated with control T cells, the infusion of CD23.CAR+ T cells resulted in a significant delay in the growth of the MEC-1 CLL cell line. These data suggest that CD23.CAR+ T cells represent a selective immunotherapy for the elimination of CD23+ leukemic cells in patients with CLL.

Original languageEnglish
Pages (from-to)4736-4745
Number of pages10
JournalBlood
Volume117
Issue number18
DOIs
Publication statusPublished - May 5 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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  • Cite this

    Attianese, G. M. P. G., Marin, V., Hoyos, V., Savoldo, B., Pizzitola, I., Tettamanti, S., Agostoni, V., Parma, M., Ponzoni, M., Bertilaccio, M. T. S., Ghia, P., Biondi, A., Dotti, G., & Biagi, E. (2011). In vitro and in vivo model of a novel immunotherapy approach for chronic lymphocytic leukemia by anti-CD23 chimeric antigen receptor. Blood, 117(18), 4736-4745. https://doi.org/10.1182/blood-2010-10-311845